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Title:
A score appraising Paleolithic diet and the risk of cardiovascular disease in a Mediterranean prospective cohort
Authors:
de la O, Víctor; Zazpe, Itziar; Goni, Leticia; Santiago, Susana; Martín-Calvo, Nerea; Bes-Rastrollo, Maira; Martínez, J. Alfredo; Martínez-González, Miguel Á.; Ruiz-Canela, Miguel
Abstract:
To assess the association between a score appraising adherence to the PaleoDiet and the risk of cardiovascular disease (CVD) in a Mediterranean cohort.
Published:
October 21, 2021
Title:
Low glycaemic diets alter lipid metabolism to influence tumour growth
Authors:
Lien, Evan C.; Westermark, Anna M.; Zhang, Yin; Yuan, Chen; Li, Zhaoqi; Lau, Allison N.; Sapp, Kiera M.; Wolpin, Brian M.; Vander Heiden, Matthew G.
Abstract:
Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth1–5. Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumour progression by lowering blood glucose and insulin levels6–8, we found that only CR inhibits the growth of select tumour allografts in mice, suggesting that other mechanisms contribute to tumour growth inhibition. A change in nutrient availability observed with CR, but not with KD, is lower lipid levels in the plasma and tumours. Upregulation of stearoyl-CoA desaturase (SCD), which synthesises monounsaturated fatty acids, is required for cancer cells to proliferate in a lipid-depleted environment, and CR also impairs tumour SCD activity to cause an imbalance between unsaturated and saturated fatty acids to slow tumour growth. Enforcing cancer cell SCD expression or raising circulating lipid levels through a higher-fat CR diet confers resistance to the effects of CR. By contrast, although KD also impairs tumour SCD activity, KD-driven increases in lipid availability maintain the unsaturated to saturated fatty acid ratios in tumours, and changing the KD fat composition to increase tumour saturated fatty acid levels cooperates with decreased tumour SCD activity to slow tumour growth. These data suggest that diet-induced mismatches between tumour fatty acid desaturation activity and the availability of specific fatty acid species determine whether low glycaemic diets impair tumour growth.
Published:
October 20, 2021
Title:
Enriching laying hens eggs by feeding diets with different fatty acid composition and antioxidants
Authors:
Vlaicu, Petru Alexandru; Panaite, Tatiana Dumitra; Turcu, Raluca Paula
Abstract:
The current study was conducted to evaluate egg quality, egg yolk fatty acids, health-related indices and antioxidants from laying hens' eggs fed different combined vegetable by-products, rich in fatty acids and antioxidants. One hundred twenty 50 weeks-old Tetra SL laying hens were divided into three groups. They were given daily a standard diet (Control, C), a diet containing 9% rapeseed meal with 3% grapeseed meal (T1 diet), or a diet containing 9% flaxseed meal and 3% sea buckthorn meal (T2 diet). Hen production performances, egg quality, egg yolk fatty acids total polyphenols content and antioxidant capacity were determined. The T1 diet significantly reduced the egg yolk content of palmitic acid from 76.615 mg (C) to 46.843 mg (T1) and that of oleic acid from 788.13 mg (C) to 682.83 mg (T1). Feeding flaxseed and sea buckthorn meals significantly increased the egg yolk content of α-linolenic acid in T2 yolks (35.297 mg) compared with C yolks (4.752 mg) and that of docosahexaenoic acid (DHA) from 16.282 mg (C) to 74.918 mg (T2). The atherogenicity indices (AI) were not significantly affected, whereas the thrombogenicity indices (TI) decreased significantly (p
Published:
October 19, 2021
Title:
Food Compass is a nutrient profiling system using expanded characteristics for assessing healthfulness of foods
Authors:
Mozaffarian, Dariush; El-Abbadi, Naglaa H.; O’Hearn, Meghan; Erndt-Marino, Josh; Masters, William A.; Jacques, Paul; Shi, Peilin; Blumberg, Jeffrey B.; Micha, Renata
Abstract:
Nutrient profiling systems (NPS) aim to discriminate the healthfulness of foods for front-of-package labelling, warning labels, taxation, company ratings and more. Existing NPS often assess relatively few nutrients and ingredients, use inconsistent criteria across food categories and have not incorporated the newest science. Here, we developed and validated an NPS, the Food Compass, to incorporate a broader range of food characteristics, attributes and uniform scoring principles. We scored 54 attributes across 9 health-relevant domains: nutrient ratios, vitamins, minerals, food ingredients, additives, processing, specific lipids, fibre and protein, and phytochemicals. The domain scores were summed into a final Food Compass Score (FCS) ranging from 1 (least healthy) to 100 (most healthy) for all foods and beverages. Content validity was confirmed by assessing nutrients, food ingredients and other characteristics of public health concern; face validity was confirmed by assessing the FCS for 8,032 foods and beverages reported in NHANES/FNDDS 2015–16; and convergent and discriminant validity was confirmed from comparisons with the NOVA food processing classification, the Health Star Rating and the Nutri-Score. The FCS differentiated food categories and food items well, with mean ± s.d. ranging from 16.4 ± 17.7 for savoury snacks and sweet desserts to 78.6 ± 17.4 for legumes, nuts and seeds. In many food categories, the FCS provided important discrimination of specific foods and beverages as compared with NOVA, the Health Star Rating or the Nutri-Score. On the basis of demonstrated content, convergent and discriminant validity, the Food Compass provides an NPS scoring a broader range of attributes and domains than previous systems with uniform and transparent principles. This publicly available tool will help guide consumer choice, research, food policy, industry reformulations and mission-focused investment decisions.
Published:
October 14, 2021
Title:
Food Compass is a nutrient profiling system using expanded characteristics for assessing healthfulness of foods
Authors:
Mozaffarian, Dariush; El-Abbadi, Naglaa H.; O’Hearn, Meghan; Erndt-Marino, Josh; Masters, William A.; Jacques, Paul; Shi, Peilin; Blumberg, Jeffrey B.; Micha, Renata
Abstract:
Nutrient profiling systems (NPS) aim to discriminate the healthfulness of foods for front-of-package labelling, warning labels, taxation, company ratings and more. Existing NPS often assess relatively few nutrients and ingredients, use inconsistent criteria across food categories and have not incorporated the newest science. Here, we developed and validated an NPS, the Food Compass, to incorporate a broader range of food characteristics, attributes and uniform scoring principles. We scored 54 attributes across 9 health-relevant domains: nutrient ratios, vitamins, minerals, food ingredients, additives, processing, specific lipids, fibre and protein, and phytochemicals. The domain scores were summed into a final Food Compass Score (FCS) ranging from 1 (least healthy) to 100 (most healthy) for all foods and beverages. Content validity was confirmed by assessing nutrients, food ingredients and other characteristics of public health concern; face validity was confirmed by assessing the FCS for 8,032 foods and beverages reported in NHANES/FNDDS 2015–16; and convergent and discriminant validity was confirmed from comparisons with the NOVA food processing classification, the Health Star Rating and the Nutri-Score. The FCS differentiated food categories and food items well, with mean ± s.d. ranging from 16.4 ± 17.7 for savoury snacks and sweet desserts to 78.6 ± 17.4 for legumes, nuts and seeds. In many food categories, the FCS provided important discrimination of specific foods and beverages as compared with NOVA, the Health Star Rating or the Nutri-Score. On the basis of demonstrated content, convergent and discriminant validity, the Food Compass provides an NPS scoring a broader range of attributes and domains than previous systems with uniform and transparent principles. This publicly available tool will help guide consumer choice, research, food policy, industry reformulations and mission-focused investment decisions.
Published:
October 14, 2021
Title:
Safety and efficacy of very low carbohydrate diet in patients with diabetic kidney disease—A randomized controlled trial
Authors:
Zainordin, Nur Aisyah; Warman, Nur’ Aini Eddy; Mohamad, Aimi Fadilah; Yazid, Fatin Aqilah Abu; Ismail, Nazrul Hadi; Chen, Xin Wee; Koshy, Marymol; Rahman, Thuhairah Hasrah Abdul; Ismail, Nafeeza Mohd; Ghani, Rohana Abdul
Abstract:
Introduction There is limited data on the effects of low carbohydrate diets on renal outcomes particularly in patients with underlying diabetic kidney disease. Therefore, this study determined the safety and effects of very low carbohydrate (VLCBD) in addition to low protein diet (LPD) on renal outcomes, anthropometric, metabolic and inflammatory parameters in patients with T2DM and underlying mild to moderate kidney disease (DKD). Materials and methods This was an investigator-initiated, single-center, randomized, controlled, clinical trial in patients with T2DM and DKD, comparing 12-weeks of low carbohydrate diet (<20g daily intake) versus standard low protein (0.8g/kg/day) and low salt diet. Patients in the VLCBD group underwent 2-weekly monitoring including their 3-day food diaries. In addition, Dual-energy x-ray absorptiometry (DEXA) was performed to estimate body fat percentages. Results The study population (n = 30) had a median age of 57 years old and a BMI of 30.68kg/m2. Both groups showed similar total calorie intake, i.e. 739.33 (IQR288.48) vs 789.92 (IQR522.4) kcal, by the end of the study. The VLCBD group showed significantly lower daily carbohydrate intake 27 (IQR25) g vs 89.33 (IQR77.4) g, p<0.001, significantly higher protein intake per day 44.08 (IQR21.98) g vs 29.63 (IQR16.35) g, p<0.05 and no difference in in daily fat intake. Both groups showed no worsening of serum creatinine at study end, with consistent declines in HbA1c (1.3(1.1) vs 0.7(1.25) %) and fasting blood glucose (1.5(3.37) vs 1.3(5.7) mmol/L). The VLCBD group showed significant reductions in total daily insulin dose (39(22) vs 0 IU, p<0.001), increased LDL-C and HDL-C, decline in IL-6 levels; with contrasting results in the control group. This was associated with significant weight reduction (-4.0(3.9) vs 0.2(4.2) kg, p =
Published:
October 13, 2021
Title:
Increase of Human Milk Fat Inducing Nutritional Ketosis in Exclusively Breastfed Infant, Brought About by Treating the Mother With Ketogenic Dietary Therapy
Authors:
Tan-Smith, Charlene; Little, Helen; Fabe, Jennifer; Dickson, Cameron; Shillito, Paul
Abstract:
Introduction:Medicalized Ketogenic Therapy is commonly used to treat refractory epilepsy. Patients have varying degrees of seizure or symptom relief, responding at individual levels of ketone production. Typically, initiating the therapy necessitates the discontinuation of breastfeeding. Our case study mother was keen to continue breastfeeding if possible. We were able to achieve this by placing the healthy mother on a ketogenic diet and altering the composition of the mother?s own milk.Main Lactation Issue:Pediatric Medicalized Ketogenic Therapy is delivered through a ketogenic diet consisting of up to 90% fat, measuring of ingredients to 0.1 g matching a food prescription of fat, protein, and carbohydrate. We placed the mother on a less stringent ketogenic diet achieving 61% fat and measured both infant and mother?s blood sugar levels and ketones. The hypothesis was that changes would occur in the mother?s own milk fat content, and/or ketones would be passed directly to the infant. If therapeutic levels of ketones were reached in the infant and a reduction in seizures observed, breastfeeding could continue.Management Overview:Over 3 months we achieved a calorific increase of the mother?s mature milk by an additional 134%. The infant was successfully put into nutritional ketosis and visible seizures eliminated.Conclusion:Medicalized Ketogenic Therapy can be safely used to treat seizures of breastfeeding infants diagnosed with epilepsy, through management of the mother on a ketogenic diet. Significantly increasing the mature mothers own milk fat component could have implications for other areas, including faltering growth.
Published:
October 5, 2021
Title:
A Novel Hypothesis Linking Low Grade Ketonemia to Cardio-Renal Benefits with SGLT2-Inhibitors
Authors:
Ekanayake, Preethika; Mudaliar, Sunder
Abstract:
The cardio-renal benefits of the SGLT2-inhibitors are well established. In 2016, we postulated that these benefits, in part, are due to the occurrence of chronic low-grade ketonemia and a shift in myocardial and renal fuel metabolism away from fat oxidation, which is energy inefficient, towards ketone oxidation, which is more energy efficient. This shift improves myocardial and renal function and can potentially translate into lower rates of progression to heart failure and end-stage kidney disease in patients with and without diabetes. There is now evidence that in addition to being an efficient fuel substrate, ketones also impart anti-inflammatory and anti-oxidative benefits on the heart and the kidney. In addition, ketones have positive effects on mitochondrial biogenesis and function, and on erythropoiesis, thereby potentially able to further ameliorate the pro-inflammatory and hypoxic milieu in those with heart and kidney failure, independent of hyperglycemia. In this review, we propose a novel hypothesis to link the pleiotropic effects of low grade ketonemia to the cardio-renal benefits seen with the SGLT2-inhibitors. This article is protected by copyright. All rights reserved.
Published:
October 4, 2021
Title:
Continuous Ketone Monitoring Consensus Report 2021
Authors:
Nguyen, Kevin T.; Xu, Nicole Y.; Zhang, Jennifer Y.; Shang, Trisha; Basu, Ananda; Bergenstal, Richard M.; Castorino, Kristin; Chen, Kong Y.; Kerr, David; Koliwad, Suneil K.; Laffel, Lori M.; Mathioudakis, Nestoras; Midyett, L. Kurt; Miller, Joshua D.; Nichols, James H.; Pasquel, Francisco J.; Prahalad, Priya; Prausnitz, Mark R.; Seley, Jane Jeffrie; Sherr, Jennifer L.; Spanakis, Elias K.; Umpierrez, Guillermo E.; Wallia, Amisha; Klonoff, David C.
Abstract:
This article is the work product of the Continuous Ketone Monitoring Consensus Panel, which was organized by Diabetes Technology Society and met virtually on April 20, 2021. The panel consisted of 20 US-based experts in the use of diabetes technology, representing adult endocrinology, pediatric endocrinology, advanced practice nursing, diabetes care and education, clinical chemistry, and bioengineering. The panelists were from universities, hospitals, freestanding research institutes, government, and private practice. Panelists reviewed the medical literature pertaining to ten topics: (1) physiology of ketone production, (2) measurement of ketones, (3) performance of the first continuous ketone monitor (CKM) reported to be used in human trials, (4) demographics and epidemiology of diabetic ketoacidosis (DKA), (5) atypical hyperketonemia, (6) prevention of DKA, (7) non-DKA states of fasting ketonemia and ketonuria, (8) potential integration of CKMs with pumps and automated insulin delivery systems to prevent DKA, (9) clinical trials of CKMs, and (10) the future of CKMs. The panelists summarized the medical literature for each of the ten topics in this report. They also developed 30 conclusions (amounting to three conclusions for each topic) about CKMs and voted unanimously to adopt the 30 conclusions. This report is intended to support the development of safe and effective continuous ketone monitoring and to apply this technology in ways that will benefit people with diabetes.
Published:
October 4, 2021
Title:
Effect of β-hydroxybutyrate monoester on markers of iron metabolism in new-onset prediabetes: findings from a randomised placebo-controlled trial
Authors:
Kimita, Wandia; Bharmal, Sakina H.; Ko, Juyeon; Cho, Jaelim; Petrov, Maxim S.
Abstract:
Background: People with prediabetes often have altered iron metabolism and may benefit from mild exogenous ketosis, which can now be successfully achieved thanks to recent developments in chemistry of food components. Objective: The objective was to investigate the effect of acute exogenous ketone monoester (β-hydroxybutyrate) on plasma levels of markers of iron metabolism in people with prediabetes. Methods: Eighteen participants with new-onset prediabetes after acute pancreatitis aged 18 years or above took part in randomised controlled cross-over trial in Auckland, New Zealand. After an overnight fast, participants consumed the exogenous ketone supplement or placebo. Blood samples were collected in the fasted state (0 minutes) and then serially every 30 minutes for 150 minutes. Both participants and study personnel were blinded to the intervention/placebo allocation. Repeated measures analysis of variance was performed using total area under the curve to determine the change in hepcidin and ferritin over time after consumption of the exogenous ketone supplement and placebo. Results: Consumption of the exogenous ketone supplement significantly elevated blood levels of β-hydroxybutyrate from 0.20 mmol L-1 at baseline to 3.50 mmol L-1 at 30 minutes (p
Published:
October 4, 2021
Title:
Short-term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross-over trial
Authors:
Walsh, Jeremy J.; Caldwell, Hannah G.; Neudorf, Helena; Ainslie, Philip N.; Little, Jonathan P.
Abstract:
Adults with obesity are at increased risk of neurocognitive impairments, partly as a result of reduced cerebral blood flow and brain-derived neurotrophic factor (BDNF). Ketone supplements containing β-hydroxybutyrate (β-OHB) are a purported therapeutic strategy for improving brain health in at-risk populations. We tested the hypothesis that short-term β-OHB supplementation will elevate cerebral blood flow and BDNF, as well as improve cognition in adults with obesity. In a placebo-controlled double-blind, cross-over design, 14 adults with obesity (10 females; aged 56 ± 12 years; body mass index = 33.8 ± 6.9 kg m-2 ) consumed 30 mL (12 g) of β-OHB or placebo thrice-daily for 14 days. Blood flow (Q) and cerebrovascular conductance (CVC) were measured in the common carotid (CCA), internal carotid (ICA) and vertebral (VA) arteries by duplex ultrasound. BDNF was measured by an enzyme-linked immunosorbent assay. Cognition was assessed by the digit-symbol substitution (DSST), Stroop and task-switching tests. Following 14 days of ketone supplementation, we observed significant improvements in cerebrovascular outcomes including QCCA (+12%), QVA (+11%), VACVC (+12%) and VA shear rate (+10%). DSST performance significantly improved following ketone supplementation (+2.7 correct responses) and improved DSST performance was positively associated improvements in cerebrovascular outcomes including QCCA , CCACVC , QVA and VACVC . By contrast to one hypothesis, β-OHB did not impact fasting serum and plasma BDNF. β-OHB supplementation improved cognition in adults with obesity, which may be partly facilitated by improvements in cerebral blood flow. β-OHB supplementation was well-tolerated and appears to be safe for cerebrovascular health, suggesting potential therapeutic benefits of β-OHB in a population at risk of neurocognitive impairment. KEY POINTS: People with obesity are at increased risk of neurocognitive dysfunction, partly as a result of -induced reductions in cerebral blood flow (CBF) and brain-derived neurotrophic factor (BDNF). Ketone supplements containing β-hydroxybutyrate (β-OHB) reduce postprandial hyperglycaemia, which may increase CBF and BDNF, thereby protecting against obesity-related cognitive dysfunction. We show for the first time that 14 days of thrice-daily β-OHB supplementation improves aspects of cognition and increases cerebrovascular flow, conductance and shear rate in the extracranial arteries of adults with obesity. Our preliminary data indicate a significant positive relationship between elevated CBF and improved cognition following β-OHB supplementation. This trial provides a foundation for the potential non-pharmacological therapeutic application of β-OHB supplementation in patient groups at risk of hyperglycaemic cerebrovascular disease and cognitive dysfunction.
Published:
October 4, 2021
Title:
Efficacy and tolerability of a whey-based, medium-chain triglyceride–enhanced ketogenic formula in children with refractory epilepsy: A retrospective study
Authors:
Wheeler, Christine E.; Temkit, M'hamed; Wilfong, Angus A.; Vanatta, Lisa; Jarrar, Randa
Abstract:
Abstract
Purpose
Ketogenic metabolic therapy (KMT) has demonstrated effectiveness in seizure reduction. However, patient compliance and adverse effects limit its use. Ready-to-feed (RTF) ketogenic formulas improve compliance and include components that mitigate adverse effects. This study is the first to evaluate the efficacy and tolerability of an RTF, whey-based, medium-chain triglyceride–enhanced (WBME) ketogenic formula.
Methods
Retrospective data from patients who received KMT between January 1, 2015, and February 28, 2018, were analyzed. Patients who received ≥75% of their total calories from the WBME formula and who were monitored for 3 months were included. Outcome measures were gastrointestinal issues, acidosis, serum blood glucose and beta-hydroxybutyrate levels, unintentional weight changes, diet response (≥50% reduction in seizures), seizure freedom, and change in formula or discontinuation of therapy. Patients with incomplete outcome data or who received <75% of total calories from the formula were excluded.
Results
Twenty-six patients (13 males; mean [SD] age, 6.1 [5.8] years) met the inclusion criteria. Thirteen patients were established patients who received a standard ketogenic formula before changing to the WBME formula; 13 were patients new to KMT whose therapy was initiated using the WBME formula. This formula was well tolerated; no patient in either group discontinued therapy or required a change in formula. The combined diet response rate (95% CI) for established and new patients was 96% (80–100%). Seizure-freedom (95% CI) for both groups at 3 months posttreatment was 20% (7–41%). The most prevalent adverse effect was constipation (69% [95% CI, 48–86%]).
Conclusion
The WBME ketogenic formula appears to be effective and well tolerated by pediatric patients with refractory epilepsy.
Published:
October 1, 2021
Title:
Ketogenic diets in the management of type 1 diabetes: Safe or safety concern?
Authors:
Buehler, Lauren Anne; Noe, Dawn; Knapp, Shannon; Isaacs, Diana; Pantalone, Kevin M.
Abstract:
The jury is still out on whether a low-carbohydrate, ketosis-inducing diet is an effective and safe adjunctive therapy to insulin in type 1 diabetes. The limited published literature reports an association with weight loss and improved glycemic control and may, over the long-term, lead to reduced macrovascular and microvascular harm. However, the attendant increased risk of dyslipidemia, diabetic ketoacidosis, and hypoglycemia warrant caution, close monitoring of patients who embark on the diet, and further research.
Published:
October 1, 2021
Title:
Microbiota-gut-brain axis: A novel potential target of ketogenic diet for epilepsy
Authors:
Tang, Yong; Wang, Qi; Liu, Jie
Abstract:
Ketogenic diet (KD) has been used to the control of seizure for 100 years because it was developed for the treatment of epilepsy in 1921. Based on current research on the microbiota-gut-brain axis to explore the new communication tool between gut bacteria and the brain and the progress of microbiota-gut-brain axis and KD for the treatment of epilepsy, the role of neurotransmitters adenosine and γ-aminobutyric acid in the epileptic brain, we propose that the balance between beneficial and harmful bacteria in the gut microbiota would be a promising target in the future to underlying the working mechanism of KD for epilepsy.
Published:
October 1, 2021
Title:
Increased somatic mutation burdens in normal human cells due to defective DNA polymerases
Authors:
Robinson, Philip S.; Coorens, Tim H. H.; Palles, Claire; Mitchell, Emily; Abascal, Federico; Olafsson, Sigurgeir; Lee, Bernard C. H.; Lawson, Andrew R. J.; Lee-Six, Henry; Moore, Luiza; Sanders, Mathijs A.; Hewinson, James; Martin, Lynn; Pinna, Claudia M. A.; Galavotti, Sara; Rahbari, Raheleh; Campbell, Peter J.; Martincorena, Iñigo; Tomlinson, Ian; Stratton, Michael R.
Abstract:
Mutation accumulation in somatic cells contributes to cancer development and is proposed as a cause of aging. DNA polymerases Pol ε and Pol δ replicate DNA during cell division. However, in some cancers, defective proofreading due to acquired POLE/POLD1 exonuclease domain mutations causes markedly elevated somatic mutation burdens with distinctive mutational signatures. Germline POLE/POLD1 mutations cause familial cancer predisposition. Here, we sequenced normal tissue and tumor DNA from individuals with germline POLE/POLD1 mutations. Increased mutation burdens with characteristic mutational signatures were found in normal adult somatic cell types, during early embryogenesis and in sperm. Thus human physiology can tolerate ubiquitously elevated mutation burdens. Except for increased cancer risk, individuals with germline POLE/POLD1 mutations do not exhibit overt features of premature aging. These results do not support a model in which all features of aging are attributable to widespread cell malfunction directly resulting from somatic mutation burdens accrued during life.
Published:
September 30, 2021
Title:
Priority micronutrient density of foods for complementary feeding of young children (6-23 months) in South and Southeast Asia
Authors:
Ortenzi, Flaminia; Beal, Ty
Abstract:
Background Given their high nutrient requirements and limited gastric capacity, young children during the complementary feeding period (6-23 months) should be fed nutrient-dense foods. However, complementary feeding diets in low- and middle-income countries are often inadequate in one or more essential micronutrients. In South and Southeast Asia infants’ and young children’s diets are commonly lacking in iron, zinc, vitamin A, folate, vitamin B12 and calcium, hereafter referred to as priority micronutrients.Objective This study aimed to identify the top food sources of priority micronutrients, among minimally processed, locally available foods, for complementary feeding of children (6-23 months) in South and Southeast Asia.Methods An aggregated regional food composition database for South and Southeast Asia was built, and recommended nutrient intakes (RNIs) from complementary foods were calculated for children aged 6-23 months. An approach was developed to classify foods into one of four levels of priority micronutrient density based on the calories and grams required to provide one-third (for individual micronutrients) or an average of one-third (for the aggregate score) of RNIs from complementary foods.Results We found that the top food sources of multiple priority micronutrients are organs, bivalves, crustaceans, fresh fish, goat, canned fish with bones, and eggs, closely followed by beef, lamb/mutton, dark green leafy vegetables, cow milk, yoghurt, and cheese, and to a lesser extent, canned fish without bones.Conclusions This analysis provided insights into which foods to prioritize to fill common micronutrient gaps and reduce undernutrition in children aged 6-23 months in South and Southeast Asia.
Published:
September 30, 2021
Title:
Ketone Ester D-β-Hydroxybutyrate-(R)-1,3 Butanediol Prevents Decline in Cardiac Function in Type 2 Diabetic Mice
Authors:
Thai, Phung N.; Miller, Charles V.; King, M. Todd; Schaefer, Saul; Veech, Richard L.; Chiamvimonvat, Nipavan; Bers, Donald M.; Dedkova, Elena N.
Abstract:
Background Heart failure is responsible for approximately 65% of deaths in patients with type 2 diabetes mellitus. However, existing therapeutics for type 2 diabetes mellitus have limited success on the prevention of diabetic cardiomyopathy. The aim of this study was to determine whether moderate elevation in D-β-hydroxybutyrate improves cardiac function in animals with type 2 diabetes mellitus. Methods and Results Type 2 diabetic (db/db) and their corresponding wild-type mice were fed a control diet or a diet where carbohydrates were equicalorically replaced by D-β-hydroxybutyrate-(R)-1,3 butanediol monoester (ketone ester [KE]). After 4 weeks, echocardiography demonstrated that a KE diet improved systolic and diastolic function in db/db mice. A KE diet increased expression of mitochondrial succinyl-CoA:3-oxoacid-CoA transferase and restored decreased expression of mitochondrial β-hydroxybutyrate dehydrogenase, key enzymes in cardiac ketone metabolism. A KE diet significantly enhanced both basal and ADP-mediated oxygen consumption in cardiac mitochondria from both wild-type and db/db animals; however, it did not result in the increased mitochondrial respiratory control ratio. Additionally, db/db mice on a KE diet had increased resistance to oxidative and redox stress, with evidence of restoration of decreased expression of thioredoxin and glutathione peroxidase 4 and less permeability transition pore activity in mitochondria. Mitochondrial biogenesis, quality control, and elimination of dysfunctional mitochondria via mitophagy were significantly increased in cardiomyocytes from db/db mice on a KE diet. The increase in mitophagy was correlated with restoration of mitofusin 2 expression, which contributed to improved coupling between cytosolic E3 ubiquitin ligase translocation into mitochondria and microtubule-associated protein 1 light chain 3-mediated autophagosome formation. Conclusions Moderate elevation in circulating D-β-hydroxybutyrate levels via KE supplementation enhances mitochondrial biogenesis, quality control, and oxygen consumption and increases resistance to oxidative/redox stress and mPTP opening, thus resulting in improvement of cardiac function in animals with type 2 diabetes mellitus.
Published:
September 29, 2021
Title:
Effects of a low-carbohydrate diet on insulin-resistant dyslipoproteinemia—a randomized controlled feeding trial
Authors:
Ebbeling, Cara B; Knapp, Amy; Johnson, Ann; Wong, Julia M W; Greco, Kimberly F; Ma, Clement; Mora, Samia; Ludwig, David S
Abstract:
Carbohydrate restriction shows promise for diabetes, but concerns regarding high saturated fat content of low-carbohydrate diets limit widespread adoption.This preplanned ancillary study aimed to determine how diets varying widely in carbohydrate and saturated fat affect cardiovascular disease (CVD) risk factors during weight-loss maintenance.After 10–14% weight loss on a run-in diet, 164 participants (70% female; BMI = 32.4 ± 4.8 kg/m2) were randomly assigned to 3 weight-loss maintenance diets for 20 wk. The prepared diets contained 20% protein and differed 3-fold in carbohydrate (Carb) and saturated fat as a proportion of energy (Low-Carb: 20% carbohydrate, 21% saturated fat; Moderate-Carb: 40%, 14%; High-Carb: 60%, 7%). Fasting plasma samples were collected prerandomization and at 20 wk. Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). Other outcomes included lipoprotein(a), triglycerides, HDL cholesterol, LDL cholesterol, adiponectin, and inflammatory markers. Repeated measures ANOVA was used for intention-to-treat analysis.Retention was 90%. Mean change in LPIR (scale 0–100) differed by diet in a dose-dependent fashion: Low-Carb (–5.3; 95% CI: –9.2, –1.5), Moderate-Carb (–0.02; 95% CI: –4.1, 4.1), High-Carb (3.6; 95% CI: –0.6, 7.7), P = 0.009. Low-Carb also favorably affected lipoprotein(a) [–14.7% (95% CI: –19.5, –9.5), –2.1 (95% CI: –8.2, 4.3), and 0.2 (95% CI: –6.0, 6.8), respectively; P = 0.0005], triglycerides, HDL cholesterol, large/very large TRL-P, large HDL-P, and adiponectin. LDL cholesterol, LDL-P, and inflammatory markers did not differ by diet.A low-carbohydrate diet, high in saturated fat, improved insulin-resistant dyslipoproteinemia and lipoprotein(a), without adverse effect on LDL cholesterol. Carbohydrate restriction might lower CVD risk independently of body weight, a possibility that warrants study in major multicentered trials powered on hard outcomes.
Published:
September 28, 2021
Title:
Ruminant fat intake improves gut microbiota, serum inflammatory parameter and fatty acid profile in tissues of Wistar rats
Authors:
de Brito Medeiros, Larissa; Alves, Susana Paula Almeida; de Bessa, Rui José Branquinho; Soares, Juliana Késsia Barbosa; Costa, Camila Neves Meireles; de Souza Aquino, Jailane; Guerra, Gerlane Coelho Bernardo; de Souza Araújo, Daline Fernandes; Toscano, Lydiane Tavares; Silva, Alexandre Sérgio; Alves, Adriano Francisco; Lemos, Mateus Lacerda Pereira; de Araujo, Wydemberg José; de Medeiros, Ariosvaldo Nunes; de Oliveira, Celso José Bruno; de Cassia Ramos do Egypto Queiroga, Rita
Abstract:
This study tested the hypothesis that naturally and industrially produced trans-fatty acids can exert distinct effects on metabolic parameters and on gut microbiota of rats. Wistar rats were randomized into three groups according to the diet: CONT-control, with 5% soybean oil and normal amount of fat; HVF-20% of hydrogenated vegetable fat (industrial); and RUM-20% of ruminant fat (natural). After 53 days of treatment, serum biochemical markers, fatty acid composition of liver, heart and adipose tissue, histology and hepatic oxidative parameters, as well as gut microbiota composition were evaluated. HVF diet intake reduced triglycerides (≈ 39.39%) and VLDL levels (≈ 39.49%). Trans-fatty acids levels in all tissue were higher in HVF group. However, RUM diet intake elevated amounts of anti-inflammatory cytokine IL-10 (≈ 14.7%) compared to CONT, but not to HVF. Furthermore, RUM intake led to higher concentrations of stearic acid and conjugated linoleic acid in all tissue; this particular diet was associated with a hepatoprotective effect. The microbial gut communities were significantly different among the groups. Our results show that ruminant fat reversed the hepatic steatosis normally caused by high fat diets, which may be related to the remodelling of the gut microbiota and its anti-inflammatory potential.
Published:
September 23, 2021
Title:
Time-restricted Eating for the Prevention and Management of Metabolic Diseases
Authors:
Manoogian, Emily N C; Chow, Lisa S; Taub, Pam R; Laferrère, Blandine; Panda, Satchidananda
Abstract:
Time-restricted feeding (TRF, animal-based studies) and time-restricted eating (TRE, humans) are an emerging behavioral intervention approach based on the understanding of the role of circadian rhythms in physiology and metabolism. In this approach, all calorie intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories. This article will summarize the origin of TRF/TRE starting with concept of circadian rhythms and the role of chronic circadian rhythm disruption in increasing the risk for chronic metabolic diseases. Circadian rhythms are usually perceived as the sleep-wake cycle and dependent rhythms arising from the central nervous system. However, the recent discovery of circadian rhythms in peripheral organs and the plasticity of these rhythms in response to changes in nutrition availability raised the possibility that adopting a consistent daily short window of feeding can sustain robust circadian rhythm. Preclinical animal studies have demonstrated proof of concept and identified potential mechanisms driving TRF-related benefits. Pilot human intervention studies have reported promising results in reducing the risk for obesity, diabetes, and cardiovascular diseases. Epidemiological studies have indicated that maintaining a consistent long overnight fast, which is similar to TRE, can significantly reduce risks for chronic diseases. Despite these early successes, more clinical and mechanistic studies are needed to implement TRE alone or as adjuvant lifestyle intervention for the prevention and management of chronic metabolic diseases.
Published:
September 22, 2021
Title:
Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis
Authors:
Trieu, Kathy; Bhat, Saiuj; Dai, Zhaoli; Leander, Karin; Gigante, Bruna; Qian, Frank; Korat, Andres V. Ardisson; Sun, Qi; Pan, Xiong-Fei; Laguzzi, Federica; Cederholm, Tommy; Faire, Ulf de; Hellénius, Mai-Lis; Wu, Jason H. Y.; Risérus, Ulf; Marklund, Matti
Abstract:
Background We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality. Methods and findings We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose–response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case–cohort, or nested case–control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≤3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels. Conclusions In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms.
Published:
September 21, 2021
Title:
Atherosclerosis
Authors:
Wang, Xinggang
Abstract:
Based on human pathology, cell biology, physics and mathematics, this paper expounds the occurrence basis of vascular diseases such as atherosclerosis. This article has a new understanding of atherosclerosis. Atherosclerosis is the result of vascular remodeling and repair.
Published:
September 20, 2021
Title:
Ketogenic diet aggravates colitis, impairs intestinal barrier and alters gut microbiota and metabolism in DSS-induced mice
Authors:
Li, Shengjie; Zhuge, Aoxiang; Wang, Kaicen; Lv, Longxian; Bian, Xiaoyuan; Yang, Liya; Xia, Jiafeng; Jiang, Xianwan; Wu, Wenrui; Wang, Shuting; Wang, Qiangqiang; Li, Lanjuan
Abstract:
Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease with a high incidence. Multiple factors including dietary composition contribute to its occurrence. Recently, ketogenic diet which consists of a high proportion of fat and low carbohydrates has gained great popularity. Our study is aimed to explore the effect of ketogenic diet on IBD and its potential mechanisms. C57BL/6 mice were given a ketogenic diet or a control diet for a month and IBD was induced by 2% DSS in drinking water in the last week. Gut histology, inflammatory cytokines and chemokines, gut microbiota and metabolism were assessed. Ketogenic diet substantially worsened colitis, in terms of higher body weight loss, DAI scores and histological scores as well as colon length shortening. Levels of serum and colon inflammatory cytokines and chemokines (IL-1α, IL-6, TNF-α, IL-17, GM-CSF and IL-10) were significantly up-regulated in mice treated with ketogenic diet and DSS. Increased intestinal permeability and decreased expressions of intestinal epithelial barrier associated genes were observed due to ketogenic diet administration. Pretreatment with ketogenic diet alters the bacterial abundance, increasing pathogenic taxa such as Proteobacteria, Enterobacteriaceae, Helicobacter and Escherichia-Shigella and decreasing potential beneficial taxa such as Erysipelotrichaceae. Ketogenic diet also modified gut metabolism, increasing metabolites in the bile secretion such as ouabain, taurochenodeoxycholic acid, quinine, cholic acid and glycocholic acid, and decreasing metabolites associated with the biosynthesis of unsaturated fatty acids including stearic acid, arachidic acid, erucic acid, and docosanoic acid. These results suggest that ketogenic diet aggravates DSS-induced colitis in mice by increasing intestinal and systemic inflammation, and disrupting the intestinal barrier, which results from modulated gut microbiota and metabolism.
Published:
September 20, 2021
Title:
Effects of a low-carbohydrate ketogenic diet on reported pain, blood biomarkers and quality of life in patients with chronic pain: A pilot randomised clinical trial
Authors:
Field, Rowena; Pourkazemi, Fereshteh; Rooney, Kieron
Abstract:
BACKGROUND: A low-carbohydrate ketogenic diet has been reported to improve chronic pain by reducing inflammation, oxidative stress, and sensitivity within the nervous system. The main aim of this trial is to evaluate the effects of a ketogenic diet on reported pain, blood biomarkers and quality of life in patients with chronic pain. METHODS: Participants with chronic musculoskeletal pain were recruited for a 12-week diet intervention that commenced with a 3-week run-in diet removing ultra-processed foods, followed by randomisation to either a whole-food/well-formulated ketogenic diet (WFKD) or to continue with the minimally processed whole-food diet (WFD). Outcome measures included: average pain (visual analogue scale VAS), blood biomarkers, anthropometrics, adherence, depression, anxiety, sleep, ketones, quality of life, diet satisfaction and macronutrient intake. RESULTS: Average weekly pain improved for both groups. WFKD group VAS reduced by 17.9 ± 5.2 mm (p = 0.004) and the WFD group VAS reduced 11.0 ± 9.0 mm (p = 0.006). Both groups also reported improved quality of life (WFKD = 11.5 ± 2.8%, p = 0.001 and WFD = 11.0 ± 3.5%, p = 0.014). The WFKD group also demonstrated significant improvements in pain interference (p = 0.013), weight (p
Published:
September 17, 2021
Title:
Steroid Hormones Affect Vascular Diseases through Myofibroblasts
Authors:
Wang, Xinggang
Abstract:
The incidence of atherosclerotic diseases in premenopausal women is lower, while the incidence of dissection or aneurysm is higher than that of men. Therefore, we generally believe that steroid hormones should have a great impact on these vascular diseases. Although this concept is widely accepted, its mechanism is still not clear. Recent studies have found that vascular diseases such as atherosclerotic diseases, aneurysm and dissection are closely related to the remodeling of myofibroblasts. Either addition or withdrawal of steroid hormones could induce apoptosis of myofibroblasts. Therefore, steroid hormones should affect vascular diseases through myofibroblasts. This paper explains the effects of steroid hormones on vascular diseases. On the one hand, the instability of steroid hormones of premenopausal women, such as estrogen and progesterone, can induce apoptosis of myofibroblasts, inhibit the remodeling of granulation tissue and alleviate intimal thickening / atherosclerotic diseases, which should be the reason why the incidence of atherosclerotic diseases in premenopausal women is lower than that among the men. On the other hand, the instability of steroid hormones also has its disadvantages. The instability of steroid hormones could lead to dysfunction of myofibroblasts and insufficient repair of granulation tissue. This in turn may increase the risk of aneurysm, dissection or unstable atherosclerotic plaques rupture. This should be one of the reasons why there are more dissections and aneurysms among premenopausal women than among men. In addition, pheochromocytoma, emotional stress, taking contraceptives, drug addict or sudden change in climates, etc. would also induce instability of steroid hormones which might account for the higher incidence of dissection, aneurysm or rupture of unstable atherosclerotic plaques . Steroid hormones should also play a similar pathophysiological role in the vascular repair of arterioles and capillaries, such as stress cardiomyopathy, nephritis, nephropathy, vasculitis, etc.
Published:
September 12, 2021
Title:
Macrophages Transform into Foam Cells by Phagocytosing Tissues Formed by Myofibroblasts
Authors:
Wang, Xinggang
Abstract:
Macrophage derived foam cells were formed by phagocytizing the tissues formed by myofibroblasts. Macrophages could inhibit, phagocytose and remodel tissues formed by myofibroblasts at early stage, which played a scavenger role in atherogenesis. This paper explains the formation of macrophage derived foam cells.
Published:
September 10, 2021
Title:
Promising Etiological Treatments of Artery Diseases
Authors:
Wang, Xinggang
Abstract:
Atherosclerotic diseases, stiffening, dissection and aneurysm are the most common artery diseases in clinical practices. Although there are many hypotheses, the pathogenesis of these diseases is unclear before. Due to unclear mechanism of these diseases before, the treatments of these diseases are still mainly based on controlling risk factors (Hypertension, Metabolic diseases, Autoimmune diseases, Smoking, etc.) and symptomatic treatments (Interventional or Surgical treatments). Our recent studies found that the occurrence of these diseases is closely related to the repair mode / degree of granulation tissue after vascular injury. These findings based on human pathology and physics can explain the characteristics of human atherosclerosis that could not be explained with the traditional hypotheses. These findings may provide promising strategies for the etiological treatments of artery diseases. In the stable conditions of artery lesions, regulating remodeling of myofibroblasts in the arteries would be likely to be an important method of etiological treatments of vascular diseases. If remodeling of myofibroblasts is in balance with vascular injury, it is an ideal state of tissue repair, and there is no need to interfere with the remodeling of myofibroblasts. However, if remodeling of myofibroblasts is in an unbalanced state, it is necessary to intervene the remodeling of myofibroblasts. It would be promising for conversion of these unbalanced lesions to balanced lesions by down-regulating remodeling of myofibroblasts in unbalanced atherosclerosis / stiffening or up-regulating remodeling of myofibroblasts in unbalanced aneurysm / dissection. Fibrosis related molecular pathways, such as TGF-β / Smad / ALK, would be promising targets for etiological treatments of these diseases.
Published:
September 10, 2021
Title:
Alaska Native Elders’ perspectives on dietary patterns in rural, remote communities
Authors:
Walch, Amanda K.; Ohle, Kathryn A.; Koller, Kathryn R.; Alexie, Lucinda; Sapp, Flora; Thomas, Timothy K.; Bersamin, Andrea
Abstract:
Given the increasing rates of childhood obesity in Alaska Native children and the understanding that the most effective interventions are informed by and reflect the cultural knowledge of the community in which they are implemented, this project sought to gather the wisdom of local Yup’ik and Cup’ik Elders in the Yukon-Kuskokwim region of Alaska around how to maintain a healthy diet and active lifestyle.
Published:
September 9, 2021
Title:
Ketone body β-hydroxybutyrate is an autophagy-dependent vasodilator
Authors:
McCarthy, Cameron G.; Chakraborty, Saroj; Singh, Gagandeep; Yeoh, Beng San; Schreckenberger, Zachary J.; Singh, Avinash; Mell, Blair; Bearss, Nicole R.; Yang, Tao; Cheng, Xi; Vijay-Kumar, Matam; Wenceslau, Camilla F.; Joe, Bina
Abstract:
Autophagy has long been associated with longevity and it is well established that autophagy reverts and prevents vascular deterioration associated with aging and cardiovascular diseases. Currently, our understanding of how autophagy benefits the vasculature is centered on the premise that reduced autophagy leads to the accumulation of cellular debris resulting in inflammation and oxidative stress, which are then reversed by reconstitution or upregulation of autophagic activity. Evolutionarily, autophagy also functions to mobilize endogenous nutrients in response to starvation. Therefore, we hypothesized that the biosynthesis of the most physiologically abundant ketone body, β-hydroxybutyrate (βHB), would be autophagy dependent, and exert vasodilatory effects via its canonical receptor, Gpr109a. We have revealed for the first time that the biosynthesis of βHB can be impaired by preventing autophagy. Subsequently, βHB caused potent vasodilation via potassium-channels, but not Gpr109a. Finally, we observed that chronic consumption of a high salt diet negatively regulates both βHB biosynthesis and hepatic autophagy, and that reconstitution of βHB bioavailability prevents high salt diet-induced endothelial dysfunction. In summary, this work offers an alternative mechanism to the anti-inflammatory and anti-oxidative stress hypothesis of autophagy-dependent vasculoprotection. Furthermore, it reveals a direct mechanism, by which ketogenic interventions (e.g., intermittent fasting) improve vascular health.
Published:
September 9, 2021
Title:
The largest and earliest known sample of dental caries in an extinct mammal (Mammalia, Euarchonta, Microsyops latidens) and its ecological implications
Authors:
Selig, Keegan R.; Silcox, Mary T.
Abstract:
Dental cavities or caries is a common disease among modern humans, affecting almost every adult. Caries frequency has been used to study dietary change in humans over time, based on an inferred tie between the incidence of caries and a carbohydrate-rich diet. However, the disease is not unique to our species. Among non-human primates, there is also variation in caries frequency associated with diet, suggesting that this metric may provide a mechanism for studying diet in broader contexts, and across geological time. To date, very few studies have examined caries among fossil mammals, and none have done so among Eocene mammals. Here, we present our analysis of the largest sample to date of fossil caries in a single extinct mammal species, Microsyops latidens, a stem primate from the early Eocene, which is known from over a thousand specimens from the Southern Bighorn Basin of Wyoming (n = 1030). Our results show that Microsyops latidens is characterized by a high prevalence of dental caries (7.48% of individuals), with notable variation through time, reaching 17.24% of individuals from a particular interval. This interval is also associated with a change in overall dental form, as quantified by dental topographic analysis, which measures functional aspects of the chewing surface of teeth. These observations suggest that this species experienced a shift in their diet to include more fruit or other sugar rich-foods for a short period. Our analysis, therefore, suggests that the diet of M. latidens fluctuated over time, as well as providing a framework for assessing caries in other fossil taxa.
Published:
September 9, 2021
Title:
Unravelling Lipoprotein Metabolism with Stable Isotopes: Tracing the Flow
Authors:
Ying, Qidi; Chan, Dick C.; Barrett, P. Hugh R.; Watts, Gerald F.
Abstract:
Dysregulated lipoprotein metabolism is a major case of atherosclerotic cardiovascular disease (ASCVD). Use of stable isotope tracers and compartmental modelling have provided deeper understanding of the mechanisms underlying lipid disorders in patients at high risk of ASCVD, including familial hypercholesterolemia (FH), elevated lipoprotein(a) [Lp(a)] and metabolic syndrome (MetS). In patients with FH, deficiency in low-density lipoprotein (LDL) receptor activity does not only impair the catabolism of LDL, but also induces hepatic overproduction and decreases catabolism of triglyceride-rich lipoproteins (TRLs). Patients with elevated Lp(a) are characterized by increased hepatic secretion of Lp(a) particles. Atherogenic dyslipidemia in MetS patients relates to a combination of overproduction of very-low density lipoprotein-apolipoprotein (apo) B-100, decreased catabolism of apoB-100-containing particles, and increased catabolism of high-density lipoprotein-apoA-I particles, as well as to impaired clearance of TRLs in the postprandial state. Kinetic studies show that weight loss, fish oils, statins and fibrates have complementary modes of action that correct atherogenic dyslipidemia. Defining the kinetic mechanisms of action of proprotein convertase subtilisin/kexin type 9 and angiopoietin-like 3 inhibitors on lipid and lipoprotein mechanism in dyslipidemic subjects will further our understanding of these therapies in decreasing the development of ASCVD. "Everything changes but change itself. Everything flows and nothing remains the same... You cannot step twice into the same river, for other waters and yet others go flowing ever on."Heraclitus (c.535- c. 475 BC).
Published:
September 8, 2021
Title:
The Physiological Control of Eating: Signals, Neurons, and Networks
Authors:
Watts, Alan G.; Kanoski, Scott E.; Sanchez-Watts, Graciela; Langhans, Wolfgang
Abstract:
During the past 30 years, investigating the physiology of eating behaviors has generated a truly vast literature. This is fueled in part by a dramatic increase in obesity and its comorbidities that has coincided with an ever increasing sophistication of genetically based manipulations. These techniques have produced results with a remarkable level of cell-specificity-particularly at the cell signaling level-and have played a lead role in advancing the field. However, putting these findings into a brain-wide context that connects physiological signals and neurons to behavior and somatic physiology requires a thorough consideration of neuronal connections; a field that has also seen an extraordinary technological revolution. Our goal is to present a comprehensive and balanced assessment of how physiological signals associated with energy homeostasis interact at many brain levels to control eating behaviors. A major theme is that these signals engage sets of interacting neural networks throughout the brain, that are defined by specific neural connections. We begin by discussing some fundamental concepts-including ones that still engender vigorous debate-that provide the necessary frameworks for understanding how the brain controls meal initiation and termination. These include: key word definitions, ATP availability as the pivotal regulated variable in energy homeostasis, neuropeptide signaling, homeostatic and hedonic eating, and meal structure. Within this context, we discuss network models of how key regions in the endbrain (or telencephalon), hypothalamus, hindbrain, medulla, vagus nerve, and spinal cord work together with the gastrointestinal tract to enable the complex motor events that permit animals to eat in diverse situations.
Published:
September 6, 2021
Title:
Clinical efficacy of eucaloric ketogenic nutrition in the COVID-19 cytokine storm: A retrospective analysis of mortality and intensive care unit admission
Authors:
Sukkar, Samir Giuseppe; Cogorno, Ludovica; Pisciotta, Livia; Pasta, Andrea; Vena, Antonio; Gradaschi, Raffaella; Dentone, Chiara; Guiddo, Erica; Martino, Eleonora; Beltramini, Sabrina; Donini, Lorenzo Maria; Carmisciano, Luca; Sormani, Maria Pia; Bassetti, Matteo
Abstract:
Objectives: Our primary objective was to explore the effect of a eucaloric ketogenic diet (EKD) on mortality, admission to the intensive care unit, and need for non-invasive ventilation in hospitalized patients with COronaVIrus Disease 19 (COVID-19), in comparison to a eucaloric standard diet. Secondary objectives were verification of the safety and feasibility of the diet and its effects on inflammatory parameters, particularly interleukin-6. Methods: The study is a retrospective analysis of 34 patients fed with an EKD in comparison to 68 patients fed with a eucaloric standard diet, selected and matched using propensity scores 1:2 to avoid the confounding effect of interfering variables. Our hypothesis was that an EKD would reduce mortality, admission to the intensive care unit, and need for non-invasive ventilation in patients with COVID-19. Results: The preliminary multivariate analysis showed a statistically significant difference in survival (P = 0.046) and need for the intensive care unit (P = 0.049) for the EKD compared with a eucaloric standard diet. Even considering the EKD start day as a time-dependent variable, the results maintain a positive trend for application of the diet, and it is not possible to reject the null hypothesis (P
Published:
September 1, 2021
Title:
Effects of low-carbohydrate diet and ketogenic diet on glucose and lipid metabolism in type 2 diabetic mice
Authors:
Yang, Zi; Mi, Jingyi; Wang, Yu; Xue, Lamei; Liu, Jinxin; Fan, Mingcong; Zhang, Duo; Wang, Li; Qian, Haifeng; Li, Yan
Abstract:
Objective With the prevalence of diabetes worldwide, it is urgent to find a suitable treatment. Recently, the ketogenic diet has shown beneficial effects in reducing blood glucose, but some concerns have been raised about its probable side effects, such as hyperlipidemia and hepatic steatosis. Because a low-carbohydrate diet replaces part of the fat with carbohydrates on the basis of the ketogenic diet, we would like to know whether it does better in treating type 2 diabetes. The aim of this study was to explore the possibility of a low-carbohydrate diet as a substitute for a ketogenic diet intervention in mice with type 2 diabetes. Methods C57 BL/6 J mice with type 2 diabetes, constructed by a high-fat diet combined with streptozotocin, were fed a standard diet, a high-fat diet, a low-carbohydrate diet, or a ketogenic diet for 14 wk, respectively. Then glucose and insulin tolerance tests were conducted. At the end of the study, blood and liver samples were collected and analyzed for serum biochemical indicators, histopathologic evaluation, hepatic lipid and glycogen content, and expression levels of mRNA and protein. Results Reduced blood glucose could be observed in both low-carbohydrate and ketogenic diets, as well as improvement in glucose tolerance and insulin sensitivity. However, the ketogenic diet decreased liver glycogen content and promoted gluconeogenesis. Mechanistically, this effect was due to inhibition of phosphorylated AMP-activated protein kinase, which could be improved by a low-carbohydrate diet. Regarding lipid metabolism, the ketogenic diet increased lipid oxidation and reduced de novo lipogenesis, but the hepatic lipid content still inevitably increased. On the contrary, the low-carbohydrate diet reduced triacylglycerols and markers of liver damage. Conclusions Collectively, these findings suggest that both diets are effective in lowering blood glucose, improving glucose tolerance, and raising insulin sensitivity. Moreover, the low-carbohydrate diet plays a role in inhibiting hepatic gluconeogenesis and improving lipid metabolism. The results suggest that the two diets have different effects on glucose and lipid metabolism, and that the low-carbohydrate diet might have more benefits in the treatment of type 2 diabetes mellitus.
Published:
September 1, 2021
Title:
Evidence of habitual behavior from non-alimentary dental wear on deciduous teeth from the Middle and Upper Paleolithic Cantabrian region, Northern Spain
Authors:
Estalrrich, Almudena; Marín-Arroyo, Ana B.
Abstract:
The use of ‘teeth as tools’ (non-masticatory or cultural-related dental wear) has largely been employed as a proxy for studying of past human behavior, mainly in permanent dentition from adult individuals. Here we present the analysis of the non-masticatory dental wear modifications on the deciduous dentition assigned to eight Neanderthal and anatomically modern human subadult individuals from Mousterian to Magdalenian technocultural contexts in the Cantabrian region (Northern Spain). Although preliminary, we tentatively suggest that these eight subadults present activity-related dental wear, including cultural striations, chipped enamel, toothpick grooves, and subvertical grooves. We also found evidence of habitual dental hygienic practices in the form of toothpicking on a deciduous premolar. Orientation of the cultural striations indicates similar handedness development as in modern children. Taken together, these dental wear patterns support the participation of young individuals in group activities, making them potential contributors to group welfare. This study potentially adds new evidence to the importance of the use of the mouth in paramasticatory activities or as a third hand throughout the Pleistocene, which can be confirmed with a more specific reference sample.
Published:
September 1, 2021
Title:
Multiproxy analysis of permafrost preserved faeces provides an unprecedented insight into the diets and habitats of extinct and extant megafauna
Authors:
Polling, Marcel; ter Schure, Anneke T. M.; van Geel, Bas; van Bokhoven, Tom; Boessenkool, Sanne; MacKay, Glen; Langeveld, Bram W.; Ariza, María; van der Plicht, Hans; Protopopov, Albert V.; Tikhonov, Alexei; de Boer, Hugo; Gravendeel, Barbara
Abstract:
The study of faecal samples to reconstruct the diets and habitats of extinct megafauna has traditionally relied on pollen and macrofossil analysis. DNA metabarcoding has emerged as a valuable tool to complement and refine these proxies. While published studies have compared the results of these three proxies for sediments, this comparison is currently lacking for permafrost preserved mammal faeces. Moreover, most metabarcoding studies have focused on a single plant-specific DNA marker region. In this study, we target both the commonly used chloroplast trnL P6 loop as well as nuclear ribosomal ITS (nrITS). The latter can increase taxonomic resolution of plant identifications but requires DNA to be relatively well preserved because of the target length (∼300–500 bp). We compare DNA results to pollen and macrofossil analyses from permafrost and ice-preserved faeces of Pleistocene and Holocene megafauna. Samples include woolly mammoth, horse, steppe bison as well as Holocene and extant caribou. Most plant identifications were found using DNA, likely because the studied faeces contained many vegetative remains that could not be identified using macrofossils or pollen. Several taxa were, however, identified to lower taxonomic levels uniquely with macrofossil and pollen analysis. The nrITS marker provides species level taxonomic resolution for commonly encountered plant families that are hard to distinguish using the other proxies (e.g. Asteraceae, Cyperaceae and Poaceae). Integrating the results from all proxies, we are able to accurately reconstruct known diets and habitats of the extant caribou. Applying this approach to the extinct mammals, we find that the Holocene horse and steppe bison were not strict grazers but mixed feeders living in a marshy wetland environment. The mammoths showed highly varying diets from different non-analogous habitats. This confirms the presence of a mosaic of habitats in the Pleistocene ‘mammoth steppe’ that mammoths could fully exploit due to their flexibility in food choice.
Published:
September 1, 2021
Title:
Dietary risk factors of primary progressive multiple sclerosis: A population-based case-control study
Authors:
Rezaeimanesh, Nasim; Moghadasi, Abdorreza Naser; Sahraian, Mohammad Ali; Eskandarieh, Sharareh
Abstract:
OBJECTIVES: There are growing evidences on the role of nutritional factors in multiple sclerosis (MS) occurrence. But dietary data are limited in primary progressive type of MS (PPMS). We assessed the role of dietary factors during adolescence in PPMS risk. METHODS: An incident case-control study on 143 PPMS cases with definite diagnosis and 400 controls were conducted in Sina hospital, Tehran, Iran. Demographic data were collected. Data on nutritional habits during adolescence were obtained using questionnaire designed for multinational case-control studies of environmental risk factors for multiple sclerosis (EnvIMS-Q). Logistic regression models were run to evaluate the role of diet in PPMS risk. RESULTS: A significant association was founded between higher intake of dairy, seafood, red meat, poultry, vegetable, fruit and nut and lower risk of PPMS (P
Published:
August 31, 2021
Title:
A non-canonical convergence of carbohydrate and glutamine metabolism is required after metabolic rewiring in 3D environment
Authors:
Wei, Peng; Bott, Alex J.; Cluntun, Ahmad A.; Morgan, Jeffrey T.; Cunningham, Corey N.; Schell, John C.; Ouyang, Yeyun; Ficarro, Scott B.; Marto, Jarrod A.; Danial, Nika N.; DeBerardinis, Ralph J.; Rutter, Jared
Abstract:
The fate of pyruvate, which is modulated mitochondrial pyruvate carrier (MPC) activity, is a defining metabolic feature in many cancers. Diffuse large B-cell lymphomas (DLBCLs) are a genetically and metabolically heterogenous cancer. Although MPC expression and activity differed between DLBCL subgroups, mitochondrial pyruvate oxidation was uniformly minimal. Mitochondrial pyruvate was instead robustly consumed by glutamate pyruvate transaminase 2 to support α-ketoglutarate production as part of glutamine catabolism. This led us to discover that glutamine exceeds pyruvate as a carbon source for the TCA cycle, but, MPC function is required to enable GPT2-mediated glutamine catabolism. Furthermore, we found that MPC inhibition only decreased DLBCL proliferation in a solid culture environment, but not in a suspension environment. Thus, the non-canonical connection between the consumption and assimilation of carbohydrates and glutamine in DLBCLs enables their proliferation in a solid 3D environment. HIGHLIGHTSMitochondrial pyruvate supports glutaminolysis in DLBCLs by supplying pyruvate for GPT2-mediated α-KG production.Glutamine, but not glucose, is a major carbon source for the TCA cycle in DLBCLs.Citrate is minimally oxidized in the TCA cycle in DLBCLs.α-KG production is important for DLBCLs proliferation in a 3D ECM environment.The mitochondrial pyruvate carrier supports DLBCL proliferation in a 3D ECM environment.
Published:
August 27, 2021
Title:
Coronary artery calcium paradox and physical activity
Authors:
Gulsin, Gaurav S.; Moss, Alastair James
Abstract:
Reducing the risk of plaque rupture events in individuals without a prior myocardial infarction is an imprecise science. To help clarify whether there is evidence of coronary artery disease and avoid ‘medicalisation’ of otherwise healthy individuals, international guidelines recommend incorporating the measurement of coronary artery calcium alongside risk prediction models.1 Coronary artery calcium serves as a surrogate marker of advanced calcified atherosclerosis and can be calculated from a non-contrast ECG-gated CT scan where a score of 1–99 Agatston units represents subclinical atherosclerosis, and a score of 100 or more Agatston units is considered an appropriate threshold for initiating medical therapy.1 At ≥100 Agatston units, the burden of advanced calcified atherosclerosis justifies statin implementation and this has been validated in a real-world cohort study of 16 996 subjects with a 10-year number needed to treat to prevent one cardiovascular event of 12.2 Many clinicians have advocated the benefits of coronary artery calcium in redefining the cardiovascular risk assessment of healthy individuals, as there is a strong link between high burdens of coronary artery calcium, accelerated progression of calcified plaque and the risk of future myocardial infarction. However, if the burden of calcified plaque is an accurate barometer of cardiovascular risk, one would expect an intervention which reduces an individual’s cardiovascular risk to attenuate progression of calcified plaque. And herein lies the coronary artery calcium paradox; both invasive and non-invasive imaging studies have …
Published:
August 27, 2021
Title:
Dairy protein intake is inversely related to development of non-alcoholic fatty liver disease
Authors:
Lee, Jun-Hyuk; Lee, Hye-Sun; Ahn, Sang Bong; Kwon, Yu-Jin
Abstract:
Summary
Background and aims
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is closely related to metabolic dysfunction, including insulin resistance, obesity, and metabolic syndrome. Dairy protein, rich in casein and whey protein, could help to reduce metabolic diseases. Therefore, we investigated the relationship between dairy protein intake and incident NAFLD.
Methods
We analyzed data for 5171 adults aged 40–69 years from the Korean Genome and Epidemiology Study. Participants were separated as men, women aged ≥50 years, and women aged −0.640. Scores were calculated as 1.18 ×metabolic syndrome (Yes: 1, No: 0) + 0.45 × diabetes mellitus (Yes: 2, No: 0) + 0.15 × serum insulin + 0.04 × AST − 0.94 × (AST/ALT) − 2.89. Cox proportional hazards spline curves were drawn to visualize dose-response relationships between dairy protein intake and incident NAFLD. Multiple Cox hazard regression analysis was conducted to examine associations between dairy protein intake and incident NAFLD.
Results
The Cox proportional hazards spline curves revealed a negative linear relationship between dairy protein intake and incident NAFLD. The cumulative incidence of NAFLD significantly decreased with increasing tertiles of dairy protein intake in men and women aged ≥50 years. After adjusting for confounding factors, the hazard ratios and 95% confidence intervals for NAFLD in the middle and highest tertiles, compared to the lowest tertile, were 0.80 (0.67–0.96) and 0.71 (0.57–0.88) in men, 0.89 (0.72–1.09) and 0.72 (0.56–0.92) in women aged ≥50 years, and 1.01 (0.80–1.27) and 0.91 (0.67–1.24) in women aged <50 years, respectively.
Conclusions
We found that higher dairy protein intake was significantly and inversely associated with the risk of incident NAFLD in men and women aged ≥50 years. Consumption of milk and other dairy products could help prevent the development of NAFLD.
Published:
August 25, 2021
Title:
Evolutionary loss of inflammasomes in the Carnivora and implications for the carriage of zoonotic infections
Authors:
Digby, Zsofi; Tourlomousis, Panagiotis; Rooney, James; Boyle, Joseph P.; Bibo-Verdugo, Betsaida; Pickering, Robert J.; Webster, Steven J.; Monie, Thomas P.; Hopkins, Lee J.; Kayagaki, Nobuhiko; Salvesen, Guy S.; Warming, Soren; Weinert, Lucy; Bryant, Clare E.
Abstract:
Zoonotic pathogens, such as COVID-19, reside in animal hosts before jumping species to infect humans. The Carnivora, like mink, carry many zoonoses, yet how diversity in host immune genes across species affect pathogen carriage is poorly understood. Here, we describe a progressive evolutionary downregulation of pathogen-sensing inflammasome pathways in Carnivora. This includes the loss of nucleotide-oligomerization domain leucine-rich repeat receptors (NLRs), acquisition of a unique caspase-1/-4 effector fusion protein that processes gasdermin D pore formation without inducing rapid lytic cell death, and the formation of a caspase-8 containing inflammasome that inefficiently processes interleukin-1β. Inflammasomes regulate gut immunity, but the carnivorous diet has antimicrobial properties that could compensate for the loss of these immune pathways. We speculate that the consequences of systemic inflammasome downregulation, however, can impair host sensing of specific pathogens such that they can reside undetected in the Carnivora.
Published:
August 24, 2021
Title:
Genetic analysis of dietary intake identifies new loci and functional links with metabolic traits
Authors:
Merino, Jordi; Dashti, Hassan S.; Sarnowski, Chloé; Lane, Jacqueline M.; Todorov, Petar V.; Udler, Miriam S.; Song, Yanwei; Wang, Heming; Kim, Jaegil; Tucker, Chandler; Campbell, John; Tanaka, Toshiko; Chu, Audrey Y.; Tsai, Linus; Pers, Tune H.; Chasman, Daniel I.; Rutter, Martin K.; Dupuis, Josée; Florez, Jose C.; Saxena, Richa
Abstract:
Dietary intake is a major contributor to the global obesity epidemic and represents a complex behavioural phenotype that is partially affected by innate biological differences. Here, we present a multivariate genome-wide association analysis of overall variation in dietary intake to account for the correlation between dietary carbohydrate, fat and protein in 282,271 participants of European ancestry from the UK Biobank (n = 191,157) and Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 91,114), and identify 26 distinct genome-wide significant loci. Dietary intake signals map exclusively to specific brain regions and are enriched for genes expressed in specialized subtypes of GABAergic, dopaminergic and glutamatergic neurons. We identified two main clusters of genetic variants for overall variation in dietary intake that were differently associated with obesity and coronary artery disease. These results enhance the biological understanding of interindividual differences in dietary intake by highlighting neural mechanisms, supporting functional follow-up experiments and possibly providing new avenues for the prevention and treatment of prevalent complex metabolic diseases.
Published:
August 23, 2021
Title:
On the nutritional and therapeutic effects of ketone body d-β-hydroxybutyrate
Authors:
Yao, Aliya; Li, Zihua; Lyu, Jinyan; Yu, Liusong; Wei, Situ; Xue, Lingyun; Wang, Hui; Chen, Guo-Qiang
Abstract:
d-β-hydroxybutyrate (d-3HB), a monomer of microbial polyhydroxybutyrate (PHB), is also a natural ketone body produced during carbohydrate deprivation to provide energy to the body cells, heart, and brain. In recent years, increasing evidence demonstrates that d-3HB can induce pleiotropic effects on the human body which are highly beneficial for improving physical and metabolic health. Conventional ketogenic diet (KD) or exogenous ketone salts (KS) and esters (KE) have been used to increase serum d-3HB level. However, strict adaptation to the KD was often associated with poor patient compliance, while the ingestion of KS caused gastrointestinal distresses due to excessive consumption of minerals. As for ingestion of KE, subsequent degradation is required before releasing d-3HB for absorption, making these methods somewhat inferior. This review provides novel insights into a biologically synthesized d-3HB (d-3-hydroxybutyric acid) which can induce a faster increase in plasma d-3HB compared to the use of KD, KS, or KE. It also emphasizes on the most recent applications of d-3HB in different fields, including its use in improving exercise performance and in treating metabolic or age-related diseases. Ketones may become a fourth micro-nutrient that is necessary to the human body along with carbohydrates, proteins, and fats. Indeed, d-3HB being a small molecule with multiple signaling pathways within the body exhibits paramount importance in mitigating metabolic and age-related diseases. Nevertheless, specific dose–response relationships and safety margins of using d-3HB remain to be elucidated with more research.
Published:
August 20, 2021
Title:
Apt interpretation of comprehensive lipoprotein data in large-scale epidemiology: disclosure of fundamental structural and metabolic relationships
Authors:
Ala-Korpela, Mika; Zhao, Siyu; Järvelin, Marjo-Riitta; Mäkinen, Ville-Petteri; Ohukainen, Pauli
Abstract:
Quantitative lipoprotein analytics using nuclear magnetic resonance (NMR) spectroscopy is currently commonplace in large-scale studies. One methodology has become widespread and is currently being utilized also in large biobanks. It allows the comprehensive characterization of 14 lipoprotein subclasses, clinical lipids, apolipoprotein A-I and B. The details of these data are conceptualized here in relation to lipoprotein metabolism with particular attention on the fundamental characteristics of subclass particle numbers, lipid concentrations and compositional measures.The NMR methodology was applied to fasting serum samples from Northern Finland Birth Cohorts 1966 and 1986 with 5651 and 5605 participants, respectively. All results were highly consistent between the cohorts. Circulating lipid concentrations in a particular lipoprotein subclass arise predominantly as the result of the circulating number of those subclass particles. The spherical lipoprotein particle shape, with a radially oriented surface monolayer, imposes size-dependent biophysical constraints for the lipid composition of individual subclass particles and inherently restricts the accommodation of metabolic changes via compositional modifications. The new finding that the relationship between lipoprotein subclass particle concentrations and the particle size is log-linear reveals that circulating lipoprotein particles are also under rather strict metabolic constraints for both their absolute and relative concentrations.The fundamental structural and metabolic relationships between lipoprotein subclasses elucidated in this study empower detailed interpretation of lipoprotein metabolism. Understanding the intricate details of these extensive data is important for the precise interpretation of novel therapeutic opportunities and for fully utilizing the potential of forthcoming analyses of genetic and metabolic data in large biobanks.
Published:
August 18, 2021
Title:
Neuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuit
Authors:
Cardoso, Filipa; Klein Wolterink, Roel G. J.; Godinho-Silva, Cristina; Domingues, Rita G.; Ribeiro, Hélder; da Silva, Joaquim Alves; Mahú, Inês; Domingos, Ana I.; Veiga-Fernandes, Henrique
Abstract:
Signals from sympathetic neurons and immune cells regulate adipocytes and thereby contribute to fat tissue biology. Interactions between the nervous and immune systems have recently emerged as important regulators of host defence and inflammation1–4. Nevertheless, it is unclear whether neuronal and immune cells co-operate in brain–body axes to orchestrate metabolism and obesity. Here we describe a neuro-mesenchymal unit that controls group 2 innate lymphoid cells (ILC2s), adipose tissue physiology, metabolism and obesity via a brain–adipose circuit. We found that sympathetic nerve terminals act on neighbouring adipose mesenchymal cells via the β2-adrenergic receptor to control the expression of glial-derived neurotrophic factor (GDNF) and the activity of ILC2s in gonadal fat. Accordingly, ILC2-autonomous manipulation of the GDNF receptor machinery led to alterations in ILC2 function, energy expenditure, insulin resistance and propensity to obesity. Retrograde tracing and chemical, surgical and chemogenetic manipulations identified a sympathetic aorticorenal circuit that modulates ILC2s in gonadal fat and connects to higher-order brain areas, including the paraventricular nucleus of the hypothalamus. Our results identify a neuro-mesenchymal unit that translates cues from long-range neuronal circuitry into adipose-resident ILC2 function, thereby shaping host metabolism and obesity.
Published:
August 18, 2021
Title:
Skeletal muscle mitochondrial network dynamics in metabolic disorders and aging
Authors:
Fealy, Ciarán E.; Grevendonk, Lotte; Hoeks, Joris; Hesselink, Matthijs K. C.
Abstract:
With global demographics trending towards an aging population, the numbers of individuals with an age-associated loss of independence is increasing. A key contributing factor is loss of skeletal muscle mitochondrial, metabolic, and contractile function. Recent advances in imaging technologies have demonstrated the importance of mitochondrial morphology and dynamics in the pathogenesis of disease. In this review, we examine the evidence for altered mitochondrial dynamics as a mechanism in age and obesity-associated loss of skeletal muscle function, with a particular focus on the available human data. We highlight some of the areas where more data are needed to identify the specific mechanisms connecting mitochondrial morphology and skeletal muscle dysfunction.
Published:
August 17, 2021
Title:
In vitro generation of oxidized standards for lipidomics. Application to major membrane lipid components
Authors:
Barker-Tejeda, Tomás Clive; Villaseñor, Alma; Gonzalez-Riano, Carolina; López-López, Ángeles; Gradillas, Ana; Barbas, Coral
Abstract:
Membrane lipids (sphingolipids, glycerophospholipids, cardiolipins, and cholesteryl esters) are critical in cellular functions. Alterations in the levels of oxidized counterparts of some of these lipids have been linked to the onset and development of many pathologies. Unfortunately, the scarce commercial availability of chemically defined oxidized lipids is a limitation for accurate quantitative analysis, characterization of oxidized composition, or testing their biological effects in lipidomic studies. To address this dearth of standards, several approaches rely on in-house prepared mixtures of oxidized species generated under in vitro conditions from different sources – non-oxidized commercial standards, liposomes, micelles, cells, yeasts, and human preparations – and using different oxidant systems – UVA radiation, air exposure, enzymatic or chemical oxidant systems, among others. Moreover, high-throughput analytical techniques such as liquid chromatography coupled to mass spectrometry (LC-MS) have provided evidence of their capabilities to study oxidized lipids both in in vitro models and complex biological samples. In this review, we describe the commercial resources currently available, the in vitro strategies carried out for obtaining oxidized lipids as standards for LC-MS analysis, and their applications in lipidomics studies, specifically for lipids found in cell and mitochondria membranes.
Published:
August 16, 2021
Title:
Daily energy expenditure through the human life course
Authors:
Pontzer, Herman; Yamada, Yosuke; Sagayama, Hiroyuki; Ainslie, Philip N.; Andersen, Lene F.; Anderson, Liam J.; Arab, Lenore; Baddou, Issaad; Bedu-Addo, Kweku; Blaak, Ellen E.; Blanc, Stephane; Bonomi, Alberto G.; Bouten, Carlijn V. C.; Bovet, Pascal; Buchowski, Maciej S.; Butte, Nancy F.; Camps, Stefan G.; Close, Graeme L.; Cooper, Jamie A.; Cooper, Richard; Das, Sai Krupa; Dugas, Lara R.; Ekelund, Ulf; Entringer, Sonja; Forrester, Terrence; Fudge, Barry W.; Goris, Annelies H.; Gurven, Michael; Hambly, Catherine; Hamdouchi, Asmaa El; Hoos, Marjije B.; Hu, Sumei; Joonas, Noorjehan; Joosen, Annemiek M.; Katzmarzyk, Peter; Kempen, Kitty P.; Kimura, Misaka; Kraus, William E.; Kushner, Robert F.; Lambert, Estelle V.; Leonard, William R.; Lessan, Nader; Martin, Corby; Medin, Anine C.; Meijer, Erwin P.; Morehen, James C.; Morton, James P.; Neuhouser, Marian L.; Nicklas, Teresa A.; Ojiambo, Robert M.; Pietiläinen, Kirsi H.; Pitsiladis, Yannis P.; Plange-Rhule, Jacob; Plasqui, Guy; Prentice, Ross L.; Rabinovich, Roberto A.; Racette, Susan B.; Raichlen, David A.; Ravussin, Eric; Reynolds, Rebecca M.; Roberts, Susan B.; Schuit, Albertine J.; Sjödin, Anders M.; Stice, Eric; Urlacher, Samuel S.; Valenti, Giulio; Etten, Ludo M. Van; Mil, Edgar A. Van; Wells, Jonathan C. K.; Wilson, George; Wood, Brian M.; Yanovski, Jack; Yoshida, Tsukasa; Zhang, Xueying; Murphy-Alford, Alexia J.; Loechl, Cornelia; Luke, Amy H.; Rood, Jennifer; Schoeller, Dale A.; Westerterp, Klaas R.; Wong, William W.; Speakman, John R.; Consortium§, IAEA DLW Database
Abstract:
A lifetime of change Measurements of total and basal energy in a large cohort of subjects at ages spanning from before birth to old age document distinct changes that occur during a human lifetime. Pontzer et al. report that energy expenditure (adjusted for weight) in neonates was like that of adults but increased substantially in the first year of life (see the Perspective by Rhoads and Anderson). It then gradually declined until young individuals reached adult characteristics, which were maintained from age 20 to 60 years. Older individuals showed reduced energy expenditure. Tissue metabolism thus appears not to be constant but rather to undergo transitions at critical junctures. Science, abe5017, this issue p. 808; see also abl4537, p. 738 Total daily energy expenditure (“total expenditure”) reflects daily energy needs and is a critical variable in human health and physiology, but its trajectory over the life course is poorly studied. We analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years. Total expenditure increased with fat-free mass in a power-law manner, with four distinct life stages. Fat-free mass–adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults. These changes shed light on human development and aging and should help shape nutrition and health strategies across the life span. A study analyzes how metabolism and energy expenditure change over the human life span. A study analyzes how metabolism and energy expenditure change over the human life span.
Published:
August 13, 2021
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