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Title:
Metabolic Strategies for Inhibiting Cancer Development
Authors:
Icard, Philippe; Loi, Mauro; Wu, Zherui; Ginguay, Antonin; Lincet, Hubert; Robin, Edouard; Coquerel, Antoine; Berzan, Diana; Fournel, Ludovic; Alifano, Marco
Abstract:
The tumor microenvironment is a complex mix of cancerous and noncancerous cells (especially immune cells and fibroblasts) with distinct metabolisms. These cells interact with each other and are influenced by the metabolic disorders of the host. In this review, we discuss how metabolic pathways that sustain biosynthesis in cancer cells could be targeted to increase the effectiveness of cancer therapies by limiting the nutrient uptake of the cell, inactivating metabolic enzymes (key regulatory ones or those linked to cell cycle progression), and inhibiting ATP production to induce cell death. Furthermore, we describe how the microenvironment could be targeted to activate the immune response by redirecting nutrients toward cytotoxic immune cells or inhibiting the release of waste products by cancer cells that stimulate immunosuppressive cells. We also examine metabolic disorders in the host that could be targeted to inhibit cancer development. To create future personalized therapies for targeting each cancer tumor, novel techniques must be developed, such as new tracers for positron emission tomography/computed tomography scan and immunohistochemical markers to characterize the metabolic phenotype of cancer cells and their microenvironment. Pending personalized strategies that specifically target all metabolic components of cancer development in a patient, simple metabolic interventions could be tested in clinical trials in combination with standard cancer therapies, such as short cycles of fasting or the administration of sodium citrate or weakly toxic compounds (such as curcumin, metformin, lipoic acid) that target autophagy and biosynthetic or signaling pathways.
Published:
February 2, 2021
Title:
Endothelial response to glucose: dysfunction, metabolism, and transport
Authors:
Clyne, Alisa Morss
Abstract:
The endothelial cell response to glucose plays an important role in both health and disease. Endothelial glucose-induced dysfunction was first studied in diabetic animal models and in cells cultured in hyperglycemia. Four classical dysfunction pathways were identified, which were later shown to result from the common mechanism of mitochondrial superoxide overproduction. More recently, non-coding RNA, extracellular vesicles, and sodium-glucose cotransporter-2 inhibitors were shown to affect glucose-induced endothelial dysfunction. Endothelial cells also metabolize glucose for their own energetic needs. Research over the past decade highlighted how manipulation of endothelial glycolysis can be used to control angiogenesis and microvascular permeability in diseases such as cancer. Finally, endothelial cells transport glucose to the cells of the blood vessel wall and to the parenchymal tissue. Increasing evidence from the blood-brain barrier and peripheral vasculature suggests that endothelial cells regulate glucose transport through glucose transporters that move glucose from the apical to the basolateral side of the cell. Future studies of endothelial glucose response should begin to integrate dysfunction, metabolism and transport into experimental and computational approaches that also consider endothelial heterogeneity, metabolic diversity, and parenchymal tissue interactions.
Published:
February 1, 2021
Title:
Impact of prolonged fasting on insulin secretion, insulin action, and hepatic versus whole body insulin secretion disposition indices in healthy young males
Authors:
Jørgensen, Sine W.; Hjort, Line; Gillberg, Linn; Justesen, Louise; Madsbad, Sten; Brøns, Charlotte; Vaag, Allan A.
Abstract:
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Published:
February 1, 2021
Title:
The Association of Lactation Duration with Visceral and Pericardial Fat Volumes in Parous Women: the CARDIA Study
Authors:
Appiah, Duke; Lewis, Cora E.; Jacobs, David R.; Shikany, James M.; Quesenberry, Charles P.; Gross, Myron; Carr, Jeff; Sidney, Stephen; Gunderson, Erica P.
Abstract:
BACKGROUND: Lactation is associated with lower risks for cardiovascular disease in women. Organ-related adiposity, which plays significant roles in the development of cardiometabolic diseases, could help explain this observation. We evaluated the association of lactation duration with visceral (VAT) and pericardial (PAT) fat volumes in women. METHODS: Data were obtained from 910 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study (1985-86) without diabetes prior to pregnancy who had ≥1 birth during 25 years of follow-up and had VAT and PAT measured from computed tomographic scans in 2010-2011. Cumulative lactation duration across all births since baseline was calculated from self-reports collected at periodic exams. RESULTS: At baseline, the average age of women (48% black, 52% white) was 24 ± 3.7 years. After controlling for baseline age, race, smoking status, body mass index, fasting glucose, family history of diabetes, fat intake, total cholesterol, physical activity and follow-up covariates (parity, gestational diabetes), the mean fat volumes across categories of lactation (none (n=221), 1 to 5 months (n=306), 6 to 11 months (n=210), and ≥12 months (n=173)) were 122.0, 113.7 105.0, and 110.1 cm3 for VAT and 52.2, 46.7, 44.5 and 43.4 cm3 for PAT, respectively. Changes in body weight from the first post-baseline birth to the end of follow-up mediated 21% and 18% of the associations of lactation with VAT and PAT, respectively. CONCLUSIONS: In this prospective study, longer cumulative lactation duration was associated with lower VAT and PAT volumes, with weight gain partially mediating these associations.
Published:
February 1, 2021
Title:
Pathologic LDL cholesterol
Authors:
Abstract:
Throughout all my investigations on the ins and outs of cholesterol, energy metabolism, diseases such as T2 diabetes, cancer, Alzheimer’s, ageing etc.. I learned a lot about the environment o…
Published:
January 31, 2021
Title:
Possible Nutrition-Related Mechanisms of Metabolic Management in Cancer Treatment
Authors:
Khodabakhshi, Adeleh; Mahmoudi, Maryam; Mehrad Majd, Hassan; Davoodi, Sayed Hossein
Abstract:
Context: Somatic mutation theory has been considered as a potential cause for cancer. However, major inconsistencies with the gene theory have necessitated serious reconsideration of this assumption. According to these inconsistencies, cancer may be considered as a metabolic disorder. According to the mitochondrial metabolic theory, substrate-level phosphorylation has been suggested to be superior to oxidative phosphorylation in cancer cells. Cancer metabolic therapies such as ketogenic diets (KD) and limitation in glutamine and calorie can be beneficial and are in line with this theory. In this study, we have reviewed the potential effects of KD as well as glutamine and calorie restriction in various types/stages of cancer with a focus on possible mechanisms. Evidence Acquisition: A comprehensive electronic search of different databases was performed using “cancer”, “ketogenic diet”, and “metabolic” as the main keywords. A comprehensive electronic search of different databases was performed using “cancer”, “ketogenic diet”, and “metabolic” as the main keywords. Results: Emerging evidence has indicated that KD can affect tumor cells by reducing glucose availability and simultaneous elevation of ketone bodies as non-fermentable metabolic fuels. KD has been suggested to be more effective as a non-toxic therapeutic measure in combination with glutamine targeting agents, chloroquine for lysosomal targeting, hyperbaric oxygen therapy, and calorie restriction. Conclusions: This metabolic approach can be considered as a promising non-toxic strategy for cancer management.
Published:
January 31, 2021
Title:
Micronutrient supplementation needs more attention in patients with refractory epilepsy under ketogenic diet treatment
Authors:
Prudencio, Mariana Baldini; de Lima, Patricia Azevedo; Murakami, Daniela Kawamoto; Sampaio, Leticia Pereira de Brito; Damasceno, Nágila Raquel Teixeira
Abstract:
OBJECTIVES: This study evaluated the adequacy of micronutrient intake from the ketogenic diet (KD) with and without micronutrient supplementation according to age in Brazilian children and adolescents with refractory epilepsy undergoing KD treatment. METHODS: This study enrolled children and adolescents with refractory epilepsy who were up to 19 y of age. Nutrient intakes were monitored using 3 d food records before introducing micronutrient supplementation and 3 mo after starting KD treatment. The prevalence of micronutrient inadequacy was estimated by sex and age according to the estimated average requirement cutoff values. RESULTS: This study included 39 children and adolescents. The KD did not provide enough content of folate, calcium, and magnesium in all patients according to the dietary reference intake. Even after starting supplementation, calcium, phosphorus, and magnesium intake remained inadequate in the majority of patients. The supplementation effectively met the vitamin B12 recommendation in all age groups. CONCLUSIONS: KD treatment did not provide adequate levels of the monitored micronutrients. The supplementation improved but did not prevent the inadequacy of micronutrients such as calcium, magnesium, and phosphorus. The results highlight the importance of individual supplementation protocols and the need to monitor micronutrient intake according to age and sex.
Published:
January 29, 2021
Title:
Obesity may exacerbate the effects of Alzheimer’s disease, new study shows | News | The University of Sheffield
Authors:
Abstract:
New research from the University of Sheffield has found being overweight is an additional burden on brain health and it may exacerbate Alzheimer’s disease.
Published:
January 29, 2021
Title:
A dietary ketone ester mitigates histological outcomes of NAFLD and markers of fibrosis in high-fat diet fed mice
Authors:
Moore, Mary P; Cunningham, Rory P; Davis, Rachel A. H.; Deemer, Sarah E.; Roberts, Brandon M.; Plaisance, Eric P.; Rector, R. Scott
Abstract:
Nutritional ketosis as a therapeutic tool has extended to the treatment of metabolic diseases including - obesity, type 2 diabetes and nonalcoholic fatty liver disease. The purpose of this study was to determine whether dietary administration of the ketone ester (KE), R,S-1,3-butanediol diacetoacetate (BD-AcAc2), attenuates markers of hepatic stellate cell (HSC) activation and hepatic fibrosis in the context of high fat diet (HFD)-induced obesity. Six-week-old male C57BL/6J mice were placed on a 10-week ad libitum HFD (45% FAT, 32% CHO, 23% PRO). Mice were then randomized to 1 of 3 groups (n = 10 per group) for an additional 12 weeks: 1) control (CON), continuous HFD, 2) pair-fed (PF) to KE; and 3) KE (HFD+30% energy from BD-AcAc2, KE). KE feeding significantly reduced histological steatosis, inflammation and total NAFLD activity score vs CON, beyond improvements observed for calorie restriction alone (PF). Dietary KE supplementation also reduced the protein content and gene expression of pro-fibrotic markers (α-SMA, Col1a1, PDGF-β, MMP9) vs CON (p 0.05). These data highlight that the dietary ketone ester, BD-AcAc2, ameliorates histological NAFLD and inflammation and reduces pro-fibrotic and pro-inflammatory markers. Future studies to further explore potential mechanisms are warranted.
Published:
January 27, 2021
Title:
A ketogenic diet consumed during radiotherapy improves several aspects of quality of life and metabolic health in women with breast cancer
Authors:
Klement, Rainer J.; Weigel, Michael M.; Sweeney, Reinhart A.
Abstract:
BACKGROUND & AIMS: Ketogenic diets (KDs) have been proposed as complementary nutritional treatments for cancer patients. Because it is important to gain knowledge about the safety of KDs adopted during cancer therapy, we studied the effects of KDs on quality of life and blood parameters in women with early-stage breast cancer undergoing radiotherapy. METHODS: A total of 29 patients consuming a KD were compared to 30 patients consuming their standard diet (SD) with respect to EORTC-QLQ30 questionnaire scores and different metabolic and hormonal blood parameters that were obtained prior to, in the middle of and at the end of radiotherapy. Baseline-to-end differences were assessed using Wilcoxon tests, and longitudinal changes were analyzed using linear mixed effects models. RESULTS: Compared to the SD, women consuming a KD experienced significant improvements in emotional functioning, social functioning, sleep quality, future perspectives and systemic therapy side effects (all p-values
Published:
January 27, 2021
Title:
Aging adipose: Depot location dictates age-associated expansion and dysfunction
Authors:
Von Bank, Helaina; Kirsh, Charlie; Simcox, Judith
Abstract:
Adipose tissue has a variety of diverse functions that maintain energy homeostasis. In conditions of excess energy availability, adipose tissue increases its lipid storage and communicates the nutritional abundance to various organs in the body. In conditions of energy depletion, such as fasting, cold exposure, or prolonged exercise, triglycerides stored in adipose tissue are released as free fatty acids to support the shift to catabolic metabolism. These diverse functions of storage, communication, and energy homeostasis are shared between numerous adipose depots including subcutaneous, visceral, brown, beige, intramuscular, marrow, and dermal adipose tissue. As organisms age, the cellular composition of these depots shifts to facilitate increased inflammatory cell infiltration, decreased vasculature, and increased adipocyte quantity and lipid droplet size. The purpose of this review is to give a comprehensive overview of the molecular and cellular changes that occur in various aged adipose depots and discuss their impact on physiology. The molecular signature of aged adipose leads to higher prevalence of metabolic disease in aged populations including type 2 diabetes, cardiovascular disease, Alzheimer's disease, and certain types of cancer.
Published:
January 27, 2021
Title:
Inceptor counteracts insulin signalling in β-cells to control glycaemia
Authors:
Ansarullah; Jain, Chirag; Far, Fataneh Fathi; Homberg, Sarah; Wißmiller, Katharina; von Hahn, Felizitas Gräfin; Raducanu, Aurelia; Schirge, Silvia; Sterr, Michael; Bilekova, Sara; Siehler, Johanna; Wiener, Julius; Oppenländer, Lena; Morshedi, Amir; Bastidas-Ponce, Aimée; Collden, Gustav; Irmler, Martin; Beckers, Johannes; Feuchtinger, Annette; Grzybek, Michal; Ahlbrecht, Christin; Feederle, Regina; Plettenburg, Oliver; Müller, Timo D.; Meier, Matthias; Tschöp, Matthias H.; Coskun, Ünal; Lickert, Heiko
Abstract:
Resistance to insulin and insulin-like growth factor 1 (IGF1) in pancreatic β-cells causes overt diabetes in mice; thus, therapies that sensitize β-cells to insulin may protect patients with diabetes against β-cell failure1–3. Here we identify an inhibitor of insulin receptor (INSR) and IGF1 receptor (IGF1R) signalling in mouse β-cells, which we name the insulin inhibitory receptor (inceptor; encoded by the gene Iir). Inceptor contains an extracellular cysteine-rich domain with similarities to INSR and IGF1R4, and a mannose 6-phosphate receptor domain that is also found in the IGF2 receptor (IGF2R)5. Knockout mice that lack inceptor (Iir−/−) exhibit signs of hyperinsulinaemia and hypoglycaemia, and die within a few hours of birth. Molecular and cellular analyses of embryonic and postnatal pancreases from Iir−/− mice showed an increase in the activation of INSR–IGF1R in Iir−/− pancreatic tissue, resulting in an increase in the proliferation and mass of β-cells. Similarly, inducible β-cell-specific Iir−/− knockout in adult mice and in ex vivo islets led to an increase in the activation of INSR–IGF1R and increased proliferation of β-cells, resulting in improved glucose tolerance in vivo. Mechanistically, inceptor interacts with INSR–IGF1R to facilitate clathrin-mediated endocytosis for receptor desensitization. Blocking this physical interaction using monoclonal antibodies against the extracellular domain of inceptor resulted in the retention of inceptor and INSR at the plasma membrane to sustain the activation of INSR–IGF1R in β-cells. Together, our findings show that inceptor shields insulin-producing β-cells from constitutive pathway activation, and identify inceptor as a potential molecular target for INSR–IGF1R sensitization and diabetes therapy.
Published:
January 27, 2021
Title:
Minireview: Effect of the ketogenic diet in excitable tissues
Authors:
Murano, Carmen; Binda, Anna; Palestini, Paola; Baruscotti, Mirko; DiFrancesco, Jacopo C; Rivolta, Ilaria
Abstract:
In the last decade Ketogenic Diet (KD) came to light as a potential treatment for a wide range of diseases, from neurological to metabolic disorders, thanks to a beneficial role mainly related to its anti-inflammatory properties. The high-fat, carbohydrate-restricted regimen causes changes in the metabolism leading, through the β-oxidation of fatty acids, to the hepatic production of ketone bodies (KBs), used by many extrahepatic tissues as energy fuels. Once synthetized, KBs move through the systemic circulation and reach all the tissues of the organism, affecting their functions and playing pleiotropic roles acting directly and indirectly on various targets as ion channels and neurotransmitters. Moreover, they can operate as signalling metabolites and epigenetic modulators. Therefore, it is limiting to consider that the clinical condition of each single patient could improve after a KD regimen based on its localized effects; rather it is more complete to think about how KBs might affect the organism as a whole. In this minireview, we tried to summarize the recent knowledge of the effects of KBs on various tissues, with a particular attention to the excitable ones, namely the nervous system, heart and muscles.
Published:
January 27, 2021
Title:
Morphological and phylogeographic evidence for budding speciation: an example in hominins
Authors:
Parins-Fukuchi, Caroline
Abstract:
Parametric phylogenetic approaches that attempt to delineate between distinct ‘modes’ of speciation (splitting cladogenesis, budding cladogenesis and anagenesis) between fossil taxa have become increasingly popular among comparative biologists. But it is not yet well understood how clearly morphological data from fossil taxa speak to detailed questions of speciation mode when compared with the lineage diversification models that serve as their basis. In addition, the congruence of inferences made using these approaches with geographical patterns has not been explored. Here, I extend a previously introduced maximum-likelihood approach for the examination of ancestor–descendant relationships to accommodate budding speciation and apply it to a dataset of fossil hominins. I place these results in a phylogeographic context to better understand spatial dynamics underlying the hypothesized speciation patterns. The spatial patterns implied by the phylogeny hint at the complex demographic processes underlying the spread and diversification of hominins throughout the Pleistocene. I also find that inferences of budding are driven primarily by stratigraphic, versus morphological, data and discuss the ramifications for interpretations of speciation process in hominins specifically and from phylogenetic data in general.
Published:
January 27, 2021
Title:
Effects of Two Months of Very Low Carbohydrate Ketogenic Diet on Body Composition, Muscle Strength, Muscle Area, and Blood Parameters in Competitive Natural Body Builders
Authors:
Paoli, Antonio; Cenci, Lorenzo; Pompei, PierLuigi; Sahin, Nese; Bianco, Antonino; Neri, Marco; Caprio, Massimiliano; Moro, Tatiana
Abstract:
Background: Ketogenic diet (KD) is a nutritional approach that restricts daily carbohydrates, replacing most of the reduced energy with fat, while maintaining an adequate quantity of protein. Despite the widespread use of KD in weight loss in athletes, there are still many concerns about its use in sports requiring muscle mass accrual. Thus, the present study sought to investigate the influence of a KD in competitive natural body builders. Methods: Nineteen volunteers (27.4 ± 10.5 years) were randomly assigned to ketogenic diet (KD) or to a western diet (WD). Body composition, muscle strength and basal metabolic rate were measured before and after two months of intervention. Standard blood biochemistry, testosterone, IGF-1, brain-derived neurotrophic factor (BDNF) and inflammatory cytokines (IL6, IL1β, TNFα) were also measured. Results: Body fat significantly decreased in KD (p = 0.030); whilst lean mass increased significantly only in WD (p < 0.001). Maximal strength increased similarly in both groups. KD showed a significant decrease of blood triglycerides (p < 0.001), glucose (p = 0.001), insulin (p < 0.001) and inflammatory cytokines compared to WD whilst BDNF increased in both groups with significant greater changes in KD (p
Published:
January 26, 2021
Title:
The Dietitian's Dilemma: What would you do if your health was restored by doing the opposite of everything you were taught?
Authors:
Hurn, Michelle; Kait, Health Coach; Gray, Dr Nevada
Abstract:
After years on a high carbohydrate diet, intense running sessions, struggling with an eating disorder, and feeling the throes of anxiety & depression, Michelle knew she needed to make a change. Does the “One size fits all” food pyramid work for everyone? Are there other options, such as a low carbohydrate or ketogenic diet that may mitigate our risk for metabolic illness and restore us to health? Could this way of eating reverse diabetes, alleviate depression, pave the way to heal eating disorders, allow us to age gracefully, and prevent heart disease? Why as a nation is our health failing, and why aren’t the nutrition guidelines updating with the science? Registered Dietitian, Michelle Hurn, dives in and offers easy to read information while covering the latest research and clinical studies. In addition, personal testimonies and actionable next steps offer hope and inspiration for you on your health journey.
Published:
January 26, 2021
Title:
The effect of paleolithic diet on glucose metabolism and lipid profile among patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials
Authors:
Sohouli, Mohammad Hassan; Fatahi, Somaye; Lari, Abolfazl; Lotfi, Mojtaba; Seifishahpar, Maryam; Găman, Mihnea-Alexandru; Rahideh, Seyedeh Tayebeh; AlBatati, Saud K.; AlHossan, Abdullah M.; Alkhalifa, Sara A.; Alomar, Sara A.; Abu-Zaid, Ahmed
Abstract:
OBJECTIVE: Several randomized clinical trials (RCTs) have investigated the effects of the Paleolithic diet (PD) in adult patients suffering from metabolic disorders. However, the results of these RCTs are conflicting. Therefore, we conducted a systematic review and meta-analysis to assess the effects of the PD in patients with metabolic disorders. METHODS: We searched the PubMed/Medline, Scopus, Cochrane Databases, Google Scholar, Web of Science, and Embase databases up to June, 2020. The data were pooled using a random-effects model. From the eligible publications, 10 articles were selected for inclusion in this systematic review and meta-analysis. The meta-analysis was performed using a random-effects model. The heterogeneity was determined using the I2 statistics and the Cochrane Q test. RESULTS: The pooled results from the random-effects model showed a significant reduction of the homeostatic model assessment of insulin resistance (HOMA-IR) (weighted mean difference, WMD: -0.39, 95% CI: -0.70, -0.08), fasting insulin (WMD: -12.17 μU/mL, 95% CI: -24.26, -0.08), total cholesterol (WMD: -0.32 mmol/l, 95% CI: -0.49, -0.15), triglycerides (WMD: -0.29 mmol/L, 95% CI: -0.42, -0.16), low-density lipoprotein cholesterol (WMD: -0.35 mmol/L, 95% CI: -0.67, -0.03), blood pressure (BP)(WMD - 5.89 mmHg; 95% CI - 9.973 to - 1.86 for the systolic BP and WMD - 4.01 mmHg; 95% CI - 6.21 to - 1.80 for the diastolic BP values) and C-reactive protein (CRP) levels (WMD: -0.84, mg/L, 95% CI: -1.62, -0.06) in the PD group versus control group. CONCLUSIONS: Our findings provide better insights into the effect of the PD on the modulation of the glucose and lipid metabolism factors in patients with metabolic disorders, providing comprehensive information for the development of future RCTs with a high quality design.
Published:
January 25, 2021
Title:
Ketogenic diet protects myelin and axons in diffuse axonal injury
Authors:
Mu, Jiao; Wang, Tingting; Li, Meiyu; Guan, Teng; Guo, Ying; Zhang, Xiaoli; Zhang, Guohui; Kong, Jiming
Abstract:
Background Ketogenic diet (KD) has been identified as a potential therapy to enhance recovery after traumatic brain injury (TBI). Diffuse axonal injury (DAI) is a common type of traumatic brain injury that is characterized by delayed axonal disconnection. Previous studies showed that demyelination resulting from oligodendrocyte damage contributes to axonal degeneration in DAI. Aim The present study tests a hypothesis that ketone bodies from the ketogenic diet confers protection for myelin and attenuates degeneration of demyelinated axon in DAI. Methods A modified Marmarou’s model of DAI was induced in adult rats. The DAI rats were fed with KD and analyzed with western blot, transmission electron microscope, ELISA test and immunohistochemistry. Meanwhile, a co-culture of primary oligodendrocytes and neurons was treated with ketone body β-hydroxybutryate (βHB) to test for its effects on the myelin-axon unit. Results Here we report that rats fed with KD showed an increased fatty acid metabolism and ketonemia. This dietary intervention significantly reduced demyelination and attenuated axonal damage in rats following DAI, likely through inhibition of DAI-induced excessive mitochondrial fission and promoting mitochondrial fusion. In an in vitro model of myelination, the ketone body βHB increased myelination significantly and reduced axonal degeneration induced by glucose deprivation (GD). βHB robustly increased cell viability, inhibited GD-induced collapse of mitochondrial membrane potential and attenuated death of oligodendrocytes. Conclusion Ketone bodies protect myelin-forming oligodendrocytes and reduce axonal damage. Ketogenic diet maybe a promising therapy for DAI.
Published:
January 23, 2021
Title:
Down syndrome is an oxidative phosphorylation disorder
Authors:
Bayona-Bafaluy, M. Pilar; Garrido-Pérez, Nuria; Meade, Patricia; Iglesias, Eldris; Jiménez-Salvador, Irene; Montoya, Julio; Martínez-Cué, Carmen; Ruiz-Pesini, Eduardo
Abstract:
Down syndrome is the most common genomic disorder of intellectual disability and is caused by trisomy of chromosome 21. Several genes in this chromosome repress mitochondrial biogenesis. The goal of this study was to evaluate whether early overexpression of these genes may cause a prenatal impairment of oxidative phosphorylation negatively affecting neurogenesis. Reduction in the mitochondrial energy production and a lower mitochondrial function have been reported in diverse tissues or cell types, and also at any age, including early fetuses, suggesting that a defect in oxidative phosphorylation is an early and general event in Down syndrome individuals. Moreover, many of the medical conditions associated with Down syndrome are also frequently found in patients with oxidative phosphorylation disease. Several drugs that enhance mitochondrial biogenesis are nowadays available and some of them have been already tested in mouse models of Down syndrome restoring neurogenesis and cognitive defects. Because neurogenesis relies on a correct mitochondrial function and critical periods of brain development occur mainly in the prenatal and early neonatal stages, therapeutic approaches intended to improve oxidative phosphorylation should be provided in these periods.
Published:
January 22, 2021
Title:
Higher Levels of Triglyceride, Fatty Acid Translocase, and Toll-Like Receptor 4 and Lower Level of HDL-C in Pregnant Women with GDM and Their Close Correlation with Neonatal Weight
Authors:
Zhou, Jianli; Bai, Jie; Guo, Yanjuan; Fu, Lijun; Xing, Jun
Abstract:
OBJECTIVES: In this study, we aimed to compare the levels of maternal blood lipids, placental and venous blood lipid transporters, and inflammatory factor receptors in pregnant women with and without gestational diabetes mellitus (GDM). We also aimed to figure out the relationship between these values and neonatal weight. METHODS: Fifty pregnant women with GDM under blood glucose control belong to the case group, and 50 pregnant women with normal glucose tolerance in concurrent delivery belong to the control group. Fasting venous blood of these pregnant women was taken 2 weeks before delivery, and umbilical cord blood was collected after delivery. The levels of triglyceride (TG), serum total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) in maternal blood and umbilical cord blood were tested in the laboratory department of our hospital. The level of toll-like receptor 4 (TLR4) in serum of umbilical veins was detected by the double-antibody sandwich ELISA. Western blot and RT-PCR were used to detect the protein and mRNA expressions of TLR4, LPL, and FAT/CD36 in the placenta. RESULTS: The level of TG in maternal blood in the case group was remarkably higher than that in the control group, which was opposite to the level of HDL-C. In the umbilical cord blood of women with GDM, the expression of TLR4 increased and was closely correlated with neonatal weight. In the placenta of women with GDM, the expressions of FAT/CD36 and TLR4 increased, and both of them were closely correlated with neonatal weight. Besides, TLR4 in umbilical cord blood increased and was closely correlated with neonatal weight. Although the expression of LPL in the placenta decreased, it had no obvious correlation with neonatal weight. CONCLUSIONS: TG in maternal blood, TLR4 in the placenta and umbilical cord blood, and FAT/CD36 in the placenta were positively correlated with neonatal weight. However, HDL-C in maternal blood was negatively correlated with neonatal weight. Although the expression of LPL in the placenta reduced due to GDM, it had no correlation with neonatal weight.
Published:
January 22, 2021
Title:
Diagnosis of obesity based on body composition-associated health risks-Time for a change in paradigm
Authors:
Bosy-Westphal, Anja; Müller, Manfred J.
Abstract:
Traditional diagnosis and understanding of the pathophysiology of obesity are based on excessive fat storage due to a chronically positive energy balance characterized by body mass index (BMI). Quantitative and qualitative analysis of lean and adipose tissue compartments by body composition analysis reveals that characterization of obesity as "overfat" does not facilitate a comprehensive understanding of obesity-associated health risk. Instead of being related to fat mass, body composition characteristics underlying BMI-associated prognosis may depend (i) on accelerated growth by a gain in lean mass or fat-free mass (FFM) in children with early BMI rebound or adolescents with early puberty; (ii) on a low muscle mass in aging, associated chronic disease, or severe illness; and (iii) on impaired adipose tissue expandability with respect to cardiometabolic risk. It is therefore time to call the adipocentric paradigm of obesity into question and to avoid the use of BMI and body fat percentage. By contrast, obesity should be seen in face of a limited FFM/muscle mass together with a limited capacity of fat storage.
Published:
January 21, 2021
Title:
Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake
Authors:
Hall, Kevin D.; Guo, Juen; Courville, Amber B.; Boring, James; Brychta, Robert; Chen, Kong Y.; Darcey, Valerie; Forde, Ciaran G.; Gharib, Ahmed M.; Gallagher, Isabelle; Howard, Rebecca; Joseph, Paule V.; Milley, Lauren; Ouwerkerk, Ronald; Raisinger, Klaudia; Rozga, Irene; Schick, Alex; Stagliano, Michael; Torres, Stephan; Walter, Mary; Walter, Peter; Yang, Shanna; Chung, Stephanie T.
Abstract:
The carbohydrate–insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m−2 were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal−1) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal−1) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d−1 less energy intake than the low-carbohydrate diet over 2 weeks (P < 0.0001) and 544 ± 68 kcal d−1 less over the final week (P
Published:
January 21, 2021
Title:
The Influence of Obesity and Associated Fatty Acids on Placental Inflammation
Authors:
Eastman, Alison J.; Moore, Rebecca E.; Townsend, Steven D.; Gaddy, Jennifer A.; Aronoff, David M.
Abstract:
PURPOSE: Maternal obesity, affecting nearly 1 in 4 pregnancies, is associated with increased circulating saturated fatty acids, such as palmitate. These fatty acids are implicated in placental inflammation, which may in turn exacerbate both maternal-fetal tolerance and responses to pathogens, such as group B Streptococcus. In this review, we address the question, "How do obesity and associated fatty acids influence placental inflammation?" METHODS: In this narrative review, we searched PubMed and Google Scholar using combinations of the key words placental inflammation or pregnancy and lipids, fatty acids, obesity, palmitate, or other closely related search terms. We also used references found within these articles that may have been absent from our original search queries. We analyzed methods and key results of these articles to compare and contrast their findings, which were occasionally at odds with each other. FINDINGS: Although obesity can be studied as a whole, complex phenomena with in vivo mouse models and human samples from patients with obesity, in vitro modeling often relies on the treatment of cells or tissues with ≥1 fatty acids and occasionally other compounds (eg, glucose and insulin). We found that palmitate, most commonly used in vitro to recreate hallmarks of obesity, induces apoptosis, oxidative stress, mitochondrial dysfunction, autophagy defects, and inflammasome activation in many placental cell types. We compare this to in vivo models of obesity wherever possible. We found that obesity as a whole may have more complex regulation of these phenomena (apoptosis, oxidative stress, mitochondrial dysfunction, autophagy defects, and inflammasome activation) compared with in vitro models of fatty acid treatment (primarily palmitate) because of the presence of unsaturated fatty acids (ie, oleate), which may have anti-inflammatory effects. IMPLICATIONS: The interaction of unsaturated fatty acids with saturated fatty acids may ameliorate many inflammatory effects of saturated fatty acids alone, which complicates interpretation of in vitro studies that focus on a particular fatty acid in isolation. This complication may explain why certain studies of obesity in vivo have differing outcomes from studies of specific fatty acids in vitro.
Published:
January 21, 2021
Title:
A Zero Carbohydrate, Carnivore Diet can Normalize Hydrogen Positive Small Intestinal Bacterial Overgrowth Lactulose Breath Tests: A Case Report
Authors:
Abstract:
Background: Small intestinal bacterial overgrowth (SIBO) is a clinical condition characterized by an excessive bacterial growth in the small intestine. Clinical symptoms might be non-specific (dyspepsia, bloating or abdominal discomfort). Nevertheless, SIBO can cause severe ma...
Published:
January 20, 2021
Title:
Beyond the Warburg Effect: Oxidative and Glycolytic Phenotypes Coexist within the Metabolic Heterogeneity of Glioblastoma
Authors:
Duraj, Tomás; García-Romero, Noemí; Carrión-Navarro, Josefa; Madurga, Rodrigo; Mendivil, Ana Ortiz de; Prat-Acin, Ricardo; Garcia-Cañamaque, Lina; Ayuso-Sacido, Angel
Abstract:
Glioblastoma (GBM) is the most aggressive primary brain tumor, with a median survival at diagnosis of 16-20 months. Metabolism represents a new attractive therapeutic target; however, due to high intratumoral heterogeneity, the application of metabolic drugs in GBM is challenging. We characterized the basal bioenergetic metabolism and antiproliferative potential of metformin (MF), dichloroacetate (DCA), sodium oxamate (SOD) and diazo-5-oxo-L-norleucine (DON) in three distinct glioma stem cells (GSCs) (GBM18, GBM27, GBM38), as well as U87MG. GBM27, a highly oxidative cell line, was the most resistant to all treatments, except DON. GBM18 and GBM38, Warburg-like GSCs, were sensitive to MF and DCA, respectively. Resistance to DON was not correlated with basal metabolic phenotypes. In combinatory experiments, radiomimetic bleomycin exhibited therapeutically relevant synergistic effects with MF, DCA and DON in GBM27 and DON in all other cell lines. MF and DCA shifted the metabolism of treated cells towards glycolysis or oxidation, respectively. DON consistently decreased total ATP production. Our study highlights the need for a better characterization of GBM from a metabolic perspective. Metabolic therapy should focus on both glycolytic and oxidative subpopulations of GSCs.
Published:
January 20, 2021
Title:
The homeoviscous adaptation to dietary lipids (HADL) model explains controversies over saturated fat, cholesterol, and cardiovascular disease risk
Authors:
Zinöcker, Marit Kolby; Svendsen, Karianne; Dankel, Simon Nitter
Abstract:
SFAs play the leading role in 1 of the greatest controversies in nutrition science. Relative to PUFAs, SFAs generally increase circulating concentrations of LDL cholesterol, a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, the purpose of regulatory mechanisms that control the diet-induced lipoprotein cholesterol dynamics is rarely discussed in the context of human adaptive biology. We argue that better mechanistic explanations can help resolve lingering controversies, with the potential to redefine aspects of research, clinical practice, dietary advice, public health management, and food policy. In this paper we propose a novel model, the homeoviscous adaptation to dietary lipids (HADL) model, which explains changes in lipoprotein cholesterol as adaptive homeostatic adjustments that serve to maintain cell membrane fluidity and hence optimal cell function. Due to the highly variable intake of fatty acids in humans and other omnivore species, we propose that circulating lipoproteins serve as a buffer to enable the rapid redistribution of cholesterol molecules between specific cells and tissues that is necessary with changes in dietary fatty acid supply. Hence, circulating levels of LDL cholesterol may change for nonpathological reasons. Accordingly, an SFA-induced raise in LDL cholesterol in healthy individuals could represent a normal rather than a pathologic response. These regulatory mechanisms may become disrupted secondarily to pathogenic processes in association with insulin resistance and the presence of other ASCVD risk factors, as supported by evidence showing diverging lipoprotein responses in healthy individuals as opposed to those with metabolic disorders such as insulin resistance and obesity. Corresponding with the model, we suggest alternative contributing factors to the association between elevated LDL cholesterol concentrations and ASCVD, involving dietary factors beyond SFAs, such as an increased endotoxin load from diet–gut microbiome interactions and subsequent chronic low-grade inflammation that interferes with fine-tuned signaling pathways.
Published:
January 20, 2021
Title:
A Zero Carbohydrate, Carnivore Diet can Normalize Hydrogen Positive Small Intestinal Bacterial Overgrowth Lactulose Breath Tests: A Case Report
Authors:
Martin, Peter; Johansson, Martina; Ek, Annelie
Abstract:
Background: Small intestinal bacterial overgrowth (SIBO) is a clinical condition characterized by an excessive bacterial growth in the small intestine. Clinical symptoms might be non-speci c (dyspepsia, bloating or abdominal discomfort). Nevertheless, SIBO can cause severe malabsorption, serious malnutrition, immune reactions, and de ciency syndromes. This retrospective case report introduces six patients with positive lactulose hydrogen SIBO breath tests. The patients chose between different therapeutic options and willingly consented to a nutritional intervention, based on a zero carbohydrate, zero bre, carnivore diet, extended over two to six weeks of time. The rationale for this dietary approach was based on the idea that opportunistic, carbohydrate favouring bacteria and methanogens proliferate in the small intestines if the natural barriers in the digestive tract have been weakened due to stress, illness, medication, etc. A zero carbohydrate, carnivore diet, consisting of animal fats and protein, could essentially eliminate these carbohydrate favouring bacteria through starvation while still providing plenty of both calories and nutrients. Methods: six patients from our functional medicine clinic followed a strict zero carb, zero ber, carnivore diet for 2-6 weeks. A lactulose breath test was performed immediately before and after the dietary change as well as extensive medical testing. Results: ve patients that followed the carnivore diet for four weeks or longer tested negative for SIBO, and the one patient that only endured the diet for two weeks had a near complete eradication of her hydrogen elevation. Methane values were generally low both before and after the dietary treatment, but there was a signi cant decrease in patients 3 and 5. Conclusions: The carbohydrate, zero bre, carnivore diet shows great potential for being a readily available, cost-effective, and equally effective alternative treatment for SIBO. According to our observations it also results in better satisfaction after meals, decreases cravings for sweets and generate weight-loss in patients where it is needed.
Published:
January 19, 2021
Title:
Ketogenic diet in women with polycystic ovary syndrome and liver dysfunction who are obese: A randomized, open-label, parallel-group, controlled pilot trial
Authors:
Li, Jian; Bai, Wen-Pei; Jiang, Bo; Bai, Le-Ran; Gu, Bei; Yan, Shu-Xiang; Li, Fu-Ying; Huang, Bin
Abstract:
AIM: To evaluate the effect of a ketogenic diet (KD) in women with polycystic ovary syndrome (PCOS) and liver dysfunction who were obese. METHODS: Women with PCOS and liver dysfunction who were obese were enrolled in this prospective, open-label, parallel-group, controlled pilot trial, and randomly received KD (KD group) or conventional pharmacological treatment (Essentiale plus Yasmin, control group) in a 1:1 ratio for 12 weeks. The primary endpoint was the liver function markers. Secondary endpoints included the menstrual cycle, anthropometric characteristics, body composition, hormonal levels, and metabolic biomarkers. RESULTS: Of the 20 eligible participants enrolled, 18 participants completed the study. The KD group reported a significant reduction in anthropometric characteristics and body composition from baseline to week 12 (all p < 0.05). In addition, there were significant reductions in menstrual cycle, plasma estradiol, and progesterone levels in two groups (all p < 0.05), but no significant between-group difference was observed. KD significantly reduced the liver function markers compared with control group (p
Published:
January 18, 2021
Title:
Effect of time restricted eating on body weight and fasting glucose in participants with obesity: results of a randomized, controlled, virtual clinical trial
Authors:
Peeke, Pamela M.; Greenway, Frank L.; Billes, Sonja K.; Zhang, Dachuan; Fujioka, Ken
Abstract:
Time restricted eating (TRE) is an emerging dietary intervention for weight loss that is hypothesized to reinforce the metabolic benefits of nightly fasting/ketosis. This pilot study investigated the effectiveness of a daily 14-h metabolic fast (14:10 TRE beginning after dinner, a “fasting snack” at hour 12, and ending with breakfast 14 h later) combined with a commercial weight management program on body weight and fasting blood glucose (FBG) in individuals with obesity. We also investigated the effect of the low-calorie, high-fat, low-carbohydrate, and low-protein “fasting snack” on blood glucose.
Published:
January 15, 2021
Title:
Role of plant-based diet in late-life cognitive decline: results from the Salus in Apulia Study
Authors:
Zupo, Roberta; Griseta, Chiara; Battista, Petronilla; Donghia, Rossella; Guerra, Vito; Castellana, Fabio; Lampignano, Luisa; Bortone, Ilaria; Lozupone, Madia; Giannelli, Gianluigi; Pergola, Giovanni De; Boeing, Heiner; Sardone, Rodolfo; Panza, Francesco
Abstract:
Objectives Consistency among population-based studies investigating the relationship between diet and cognition in older inhabitants in the Mediterranean area is poor. The present study investigated whether diet changes over 12 years were associated with cognitive function in older people in Southern-Italy. Methods From the ‘Salus in Apulia Study’, that includes the MICOL and GreatAGE Studies, 584 participants were selected, firstly enrolled in MICOL3 (M3) and later in the GreatAGE Study (MICOL4, M4). Foods and micronutrients intake were recorded in both studies, and global cognitive function in M4, assessed with the Mini Mental State Examination. Results Plant-based foods, particularly coffee and vegetables, as well as vitamin A sources, were inversely associated to age-related cognitive impairment. Alcohol consumption showed a detrimental role on cognition, while red meat appeared to be beneficial in the present study, although its role is traditionally considered harmful for cognitive function. Discussion Our study confirmed that a traditional Mediterranean dietary pattern based on agricultural products and low alcohol consumption may help to prevent/delay age-related cognitive impairment.
Published:
January 15, 2021
Title:
Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data
Authors:
Goldenberg, Joshua Z.; Day, Andrew; Brinkworth, Grant D.; Sato, Junko; Yamada, Satoru; Jönsson, Tommy; Beardsley, Jennifer; Johnson, Jeffrey A.; Thabane, Lehana; Johnston, Bradley C.
Abstract:
Objective To determine the efficacy and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes. Design Systematic review and meta-analysis. Data sources Searches of CENTRAL, Medline, Embase, CINAHL, CAB, and grey literature sources from inception to 25 August 2020. Study selection Randomized clinical trials evaluating LCDs (<130 g/day or <26% of a 2000 kcal/day diet) and VLCDs (<10% calories from carbohydrates) for at least 12 weeks in adults with type 2 diabetes were eligible. Data extraction Primary outcomes were remission of diabetes (HbA1c <6.5% or fasting glucose <7.0 mmol/L, with or without the use of diabetes medication), weight loss, HbA1c, fasting glucose, and adverse events. Secondary outcomes included health related quality of life and biochemical laboratory data. All articles and outcomes were independently screened, extracted, and assessed for risk of bias and GRADE certainty of evidence at six and 12 month follow-up. Risk estimates and 95% confidence intervals were calculated using random effects meta-analysis. Outcomes were assessed according to a priori determined minimal important differences to determine clinical importance, and heterogeneity was investigated on the basis of risk of bias and seven a priori subgroups. Any subgroup effects with a statistically significant test of interaction were subjected to a five point credibility checklist. Results Searches identified 14 759 citations yielding 23 trials (1357 participants), and 40.6% of outcomes were judged to be at low risk of bias. At six months, compared with control diets, LCDs achieved higher rates of diabetes remission (defined as HbA1c <6.5%) (76/133 (57%) v 41/131 (31%); risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264, I2=58%). Conversely, smaller, non-significant effect sizes occurred when a remission definition of HbA1c
Published:
January 13, 2021
Title:
Mammal species occupy different climates following the expansion of human impacts
Authors:
Pineda-Munoz, Silvia; Wang, Yue; Lyons, S. Kathleen; Tóth, Anikó B.; McGuire, Jenny L.
Abstract:
Cities and agricultural fields encroach on the most fertile, habitable terrestrial landscapes, fundamentally altering global ecosystems. Today, 75% of terrestrial ecosystems are considerably altered by human activities, and landscape transformation continues to accelerate. Human impacts are one of the major drivers of the current biodiversity crisis, and they have had unprecedented consequences on ecosystem function and rates of species extinctions for thousands of years. Here we use the fossil record to investigate whether changes in geographic range that could result from human impacts have altered the climatic niches of 46 species covering six mammal orders within the contiguous United States. Sixty-seven percent of the studied mammals have significantly different climatic niches today than they did before the onset of the Industrial Revolution. Niches changed the most in the portions of the range that overlap with human-impacted landscapes. Whether by forcible elimination/introduction or more indirect means, large-bodied dietary specialists have been extirpated from climatic envelopes that characterize human-impacted areas, whereas smaller, generalist mammals have been facilitated, colonizing these same areas of the climatic space. Importantly, the climates where we find mammals today do not necessarily represent their past habitats. Without mitigation, as we move further into the Anthropocene, we can anticipate a low standing biodiversity dominated by small, generalist mammals.
Published:
January 12, 2021
Title:
Comparing effectiveness of fat burners and thermogenic supplements to diet and exercise for weight loss and cardiometabolic health: Systematic review and meta-analysis
Authors:
Clark, James E.; Welch, Sarah
Abstract:
BACKGROUND: Those who are overfat face an onslaught of advice for losing weight, including using dietary supplements that purport to have fat burning capabilities to achieve a reduced body mass, fat mass and improvement in cardiometabolic health in combination with exercise or diet and exercise regimens. AIM: To examine long-term effectiveness of supplements for both weight loss and improvements in cardiometabolic health for these individuals. METHODS: A PRISMA methods of systematic review was conducted from August 2018 through January 2019 using Medline, PubChem, PubMed, EBOSCO CINHAL and SPORTDiscus, and Google Scholar yielding 23,441 returns of which 21 studies (duration greater than 8 weeks with participant populations of BMI greater than 24.9) were included for meta-analysis. Meta-analysis examined pooled effect size and 95% confidence interval for: body mass, fat mass, fat-free mass, total cholesterol, high-density lipoproteins, low-density lipoproteins, resting metabolic rate. Intra-study effect sizes were compared with previously reported results for diet or diet and exercise in a 2x2 chi-square analysis for the number of studies that induced effects greater than or less than the effect size. RESULTS: There is a general trend to show effectiveness (effect size greater than 0.00) for obtaining beneficial changes from use of thermogenic dietary supplements, yet the 95% confidence interval for effect size crossed 0.00 (indicating no benefit). Chi-square comparison to exercise, or combination of diet and exercise, indicates that responses induced from weight-loss supplements were less effective than what is obtained from utilizing exercise, or diet and exercise, without additional weight-loss supplements. CONCLUSION: There appears to be limited benefit that may be derived from the inclusion of thermogenic dietary supplements to reduce body mass and improve cardiometabolic health for individuals who are overfat.
Published:
January 11, 2021
Title:
Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals
Authors:
Asnicar, Francesco; Berry, Sarah E.; Valdes, Ana M.; Nguyen, Long H.; Piccinno, Gianmarco; Drew, David A.; Leeming, Emily; Gibson, Rachel; Le Roy, Caroline; Khatib, Haya Al; Francis, Lucy; Mazidi, Mohsen; Mompeo, Olatz; Valles-Colomer, Mireia; Tett, Adrian; Beghini, Francesco; Dubois, Léonard; Bazzani, Davide; Thomas, Andrew Maltez; Mirzayi, Chloe; Khleborodova, Asya; Oh, Sehyun; Hine, Rachel; Bonnett, Christopher; Capdevila, Joan; Danzanvilliers, Serge; Giordano, Francesca; Geistlinger, Ludwig; Waldron, Levi; Davies, Richard; Hadjigeorgiou, George; Wolf, Jonathan; Ordovás, José M.; Gardner, Christopher; Franks, Paul W.; Chan, Andrew T.; Huttenhower, Curtis; Spector, Tim D.; Segata, Nicola
Abstract:
The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease.
Published:
January 11, 2021
Title:
Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals
Authors:
Asnicar, Francesco; Berry, Sarah E.; Valdes, Ana M.; Nguyen, Long H.; Piccinno, Gianmarco; Drew, David A.; Leeming, Emily; Gibson, Rachel; Roy, Caroline Le; Khatib, Haya Al; Francis, Lucy; Mazidi, Mohsen; Mompeo, Olatz; Valles-Colomer, Mireia; Tett, Adrian; Beghini, Francesco; Dubois, Léonard; Bazzani, Davide; Thomas, Andrew Maltez; Mirzayi, Chloe; Khleborodova, Asya; Oh, Sehyun; Hine, Rachel; Bonnett, Christopher; Capdevila, Joan; Danzanvilliers, Serge; Giordano, Francesca; Geistlinger, Ludwig; Waldron, Levi; Davies, Richard; Hadjigeorgiou, George; Wolf, Jonathan; Ordovás, José M.; Gardner, Christopher; Franks, Paul W.; Chan, Andrew T.; Huttenhower, Curtis; Spector, Tim D.; Segata, Nicola
Abstract:
The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease. Analyses from the gut microbiome of over 1,000 individuals from the PREDICT 1 study, for which detailed long-term diet information as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements are available, unveil new associations between specific gut microbes, dietary habits and cardiometabolic health.
Published:
January 11, 2021
Title:
Long-term association of red meat consumption and lipid profile: A 13-year prospective population-based cohort study
Authors:
Hassannejad, Razieh; Moosavian, Seyedeh Parisa; Mohammadifard, Noushin; Mansourian, Marjan; Roohafza, Hamidreza; Sadeghi, Masoumeh; Sarrafzadegan, Nizal
Abstract:
OBJECTIVES: The long-term associations between red meat consumption and lipid profile are not completely known. This longitudinal study assessed the association of red meat consumption with lipid profile in healthy Iranian adults using repeated measurements of red meat intake. METHODS: The population-based longitudinal study was conducted within the framework of the Isfahan Cohort Study on a subsample of 1376 healthy adults, aged ≥35 y, for whom complete information was available in all three phases of the study. A simplified qualitative 48-item food frequency questionnaire, blood pressure, anthropometric measurements, and fasting serum lipids and blood sugar were evaluated in three phases. Mixed-effects linear regression was applied to examine the longitudinal associations between red meat consumption and lipid profile. RESULTS: After adjustment for potential confounders, each single-serving increase in red meat and organ meat consumption was significantly associated with an increment in triacylglycerol (β = 6.30; 95% confidence interval [CI], 3.97-8.63), total cholesterol (β = 3.03; 95% CI, 2.02-4.04), low-density lipoprotein (β = 3.40; 95% CI, 2.64-4.17), high-density lipoprotein (β = 0.60; 95% CI, 0.28-0.93), ratio of low-density to high-density lipoprotein (β = 0.03; 95% CI, 0.01-0.05), and non-high-density lipoprotein (β = 2.42; 95% CI, 1.41-3.43). However, processed meat consumption had no significant association with lipid profile. CONCLUSIONS: Total red meat intake had a significant, direct association with lipid profile after a 13-year follow-up period in a cohort of the healthy Iranian population.
Published:
January 10, 2021
Title:
Metabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse model
Authors:
Maeyama, Masahiro; Tanaka, Kazuhiro; Nishihara, Masamitsu; Irino, Yasuhiro; Shinohara, Masakazu; Nagashima, Hiroaki; Tanaka, Hirotomo; Nakamizo, Satoshi; Hashiguchi, Mitsuru; Fujita, Yuichi; Kohta, Masaaki; Kohmura, Eiji; Sasayama, Takashi
Abstract:
The ketogenic diet (KD) is a high fat and low carbohydrate diet that produces ketone bodies through imitation of starvation. The combination of KD and Bevacizumab (Bev), a VEGF inhibitor, is considered to further reduce the supply of glucose to the tumor. The metabolite changes in U87 glioblastoma mouse models treated with KD and/or Bev were examined using gas chromatography-mass spectrometry. The combination therapy of KD and Bev showed a decrease in the rate of tumor growth and an increase in the survival time of mice, although KD alone did not have survival benefit. In the metabolome analysis, the pattern of changes for most amino acids are similar between tumor and brain tissues, however, some amino acids such as aspartic acid and glutamic acid were different between tumors and brain tissues. The KD enhanced the anti-tumor efficacy of Bev in a glioblastoma intracranial implantation mouse model, based on lowest levels of microvascular density (CD31) and cellular proliferation markers (Ki-67 and CCND1) in KD + Bev tumors compared to the other groups. These results suggested that KD combined with Bev may be a useful treatment strategy for patients with GBM.
Published:
January 8, 2021
Title:
The new European guidelines for prevention of cardiovascular disease are misleading
Authors:
Ravnskov, Uffe; Alabdulgader, Abdullah; de Lorgeril, Michel; Diamond, David M.; Hama, Rokuro; Hamazaki, Tomohito; Hammarskjöld, Björn; Harcombe, Zoe; Kendrick, Malcolm; Langsjoen, Peter; McCully, Kilmer S.; Okuyama, Harumi; Sultan, Sherif; Sundberg, Ralf
Abstract:
Introduction: The European Society of Cardiology and European Atherosclerosis Society (ESC/EAS) have recently published three major revisions of their guidelines for the management of chronic heart disease, blood lipids, and diabetes. Areas covered: We have scrutinized these guidelines in detail and found that the authors have ignored many studies that are in conflict with their conclusions and recommendations. Expert commentary: The authors of the guidelines have ignored that LDL-cholesterol (LDL-C) of patients with acute myocardial infarction is lower than normal; that high cholesterol is not a risk factor for diabetics; that the degree of coronary artery calcification is not associated with LDL-C; and that 27 follow-up studies have shown that people with high total cholesterol or LDL-C live just as long or longer than people with low cholesterol. They have also ignored the lack of exposure-response in the statin trials; that several of these trials have been unable to lower CVD or total mortality; that no statin trial has succeeded with lowering mortality in women, elderly people, or diabetics; and that cholesterol-lowering with statins has been associated with many serious side effects.
Published:
January 8, 2021
Title:
Excess protein enabled dog domestication during severe Ice Age winters
Authors:
Lahtinen, Maria; Clinnick, David; Mannermaa, Kristiina; Salonen, J. Sakari; Viranta, Suvi
Abstract:
Dogs (Canis familiaris) are the first animals to be domesticated by humans and the only ones domesticated by mobile hunter-gatherers. Wolves and humans were both persistent, pack hunters of large prey. They were species competing over resources in partially overlapping ecological niches and capable of killing each other. How could humans possibly have domesticated a competitive species? Here we present a new hypothesis based on food/resource partitioning between humans and incipient domesticated wolves/dogs. Humans are not fully adapted to a carnivorous diet; human consumption of meat is limited by the liver’s capacity to metabolize protein. Contrary to humans, wolves can thrive on lean meat for months. We present here data showing that all the Pleistocene archeological sites with dog or incipient dog remains are from areas that were analogous to subarctic and arctic environments. Our calculations show that during harsh winters, when game is lean and devoid of fat, Late Pleistocene hunters-gatherers in Eurasia would have a surplus of animal derived protein that could have been shared with incipient dogs. Our partitioning theory explains how competition may have been ameliorated during the initial phase of dog domestication. Following this initial period, incipient dogs would have become docile, being utilized in a multitude of ways such as hunting companions, beasts of burden and guards as well as going through many similar evolutionary changes as humans.
Published:
January 7, 2021
Title:
ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism
Authors:
Qi, Guoyuan; Mi, Yashi; Shi, Xiaojian; Gu, Haiwei; Brinton, Roberta Diaz; Yin, Fei
Abstract:
Alzheimer's disease (AD) risk gene ApoE4 perturbs brain lipid homeostasis and energy transduction. However, the cell-type-specific mechanism of ApoE4 in modulating brain lipid metabolism is unclear. Here, we describe a detrimental role of ApoE4 in regulating fatty acid (FA) metabolism across neuron and astrocyte in tandem with their distinctive mitochondrial phenotypes. ApoE4 disrupts neuronal function by decreasing FA sequestering in lipid droplets (LDs). FAs in neuronal LDs are exported and internalized by astrocytes, with ApoE4 diminishing the transport efficiency. Further, ApoE4 lowers FA oxidation and leads to lipid accumulation in both astrocyte and the hippocampus. Importantly, diminished capacity of ApoE4 astrocytes in eliminating neuronal lipids and degrading FAs accounts for their compromised metabolic and synaptic support to neurons. Collectively, our findings reveal a mechanism of ApoE4 disruption to brain FA and bioenergetic homeostasis that could underlie the accelerated lipid dysregulation and energy deficits and increased AD risk for ApoE4 carriers.
Published:
January 5, 2021
Title:
Differences in taste and smell perception between type 2 diabetes mellitus patients and healthy controls
Authors:
Catamo, Eulalia; Tornese, Gianluca; Concas, Maria P.; Gasparini, Paolo; Robino, Antonietta
Abstract:
BACKGROUND AND AIMS: The senses of taste and smell are essential determinants of food choice, which in turn may contribute to the development of chronic diseases, including diabetes. Although past studies have evaluated the relationship between type 2 diabetes mellitus (DM2) and senses disorders, this relationship remains controversial. In this study, we evaluated taste and smell perception in DM2 patients and healthy controls (HC). Moreover, we analyzed the association of chemosensory impairments with anthropometric and clinical outcomes (e.g. Body Mass Index (BMI), Fasting blood glucose (FBG), drugs, cardiovascular diseases (CVD), and hypertension) in DM2 patients. METHODS AND RESULTS: The study included 94 DM2 patients and 244 HC. Taste recognition for 6-n-propylthiouracil (PROP), quinine, citric acid, sucrose, and sodium chloride (NaCl) compounds was assessed using a filter paper method, while smell recognition of 12 odorants was performed using a Sniffin' sticks test. We found that a higher percentage of DM2 patients showed identification impairment in salt taste (22% vs. 5%, p-value
Published:
January 4, 2021
Title:
Integrated genomic and transcriptomic analysis reveals unique characteristics of hepatic metastases and pro-metastatic role of complement C1q in pancreatic ductal adenocarcinoma
Authors:
Yang, Jianyu; Lin, Ping; Yang, Minwei; Liu, Wei; Fu, Xueliang; Liu, Dejun; Tao, Lingye; Huo, Yanmiao; Zhang, Junfeng; Hua, Rong; Zhang, Zhigang; Li, Yixue; Wang, Liwei; Xue, Jing; Li, Hong; Sun, Yongwei
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers due to its high metastasis rate in the liver. However, little is known about the molecular features of hepatic metastases due to difficulty in obtaining fresh tissues and low tumor cellularity.
Published:
January 4, 2021
Title:
Integrated genomic and transcriptomic analysis reveals unique characteristics of hepatic metastases and pro-metastatic role of complement C1q in pancreatic ductal adenocarcinoma
Authors:
Yang, Jianyu; Lin, Ping; Yang, Minwei; Liu, Wei; Fu, Xueliang; Liu, Dejun; Tao, Lingye; Huo, Yanmiao; Zhang, Junfeng; Hua, Rong; Zhang, Zhigang; Li, Yixue; Wang, Liwei; Xue, Jing; Li, Hong; Sun, Yongwei
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers due to its high metastasis rate in the liver. However, little is known about the molecular features of hepatic metastases due to difficulty in obtaining fresh tissues and low tumor cellularity.
Published:
January 4, 2021
Title:
Environmental factors and epidemiology of childhood type 1 diabetes
Authors:
Lukács, Krisztina; Pánczél, Pál; Hosszúfalusi, Nóra
Abstract:
Összefoglaló. A Nemzetközi Diabetes Szövetség (International Diabetes Federation, IDF) legutóbbi becslése szerint napjainkban több mint 600 000, 15 év alatti 1-es típusú cukorbeteg gyermek él a világon, az új esetek száma pedig évi 98 200-ra tehető. Az elmúlt évtizedekben az 1-es típusú diabetes incidenciája világszerte jelentősen nőtt ebben a korosztályban: Európában az 1989 és 2013 közötti periódusban átlagosan évi 3,4%-kal, ami 20 éven belül a betegek számának duplázódását vetíti előre a kontinensen. Az epidemiológiai vizsgálatok kezdete óta nyilvánvaló, hogy a gyermekkori kezdetű, 1-es típusú diabetes előfordulási gyakorisága széles határok között ingadozik, amit egyaránt befolyásolnak geográfiai és klímaviszonyok, etnikai és demográfiai hatások. Bár az 1-es típusú cukorbetegség kialakulása során az autoimmunitás primer kockázati tényezője a genetikai háttér, mégsem a genetikai terheltség populációszintű fokozódása okozza az incidencia robbanásszerű növekedését, hanem a környezeti tényezőknek a betegség penetranciáját megváltoztató hatása. A környezeti hatások oki tényezőkként, akcelerátorokként és védőfaktorokként is hozzájárulhatnak mindehhez, sőt akár a betegség patogenezisében egyszerre több ponton, több mechanizmussal is részt vehetnek. Ugyanakkor a nemzetközi kutatások ellenére a legnépszerűbb háttérelméletek (például vírusinfekció, higiéniahipotézis, bélmikrobiom, áteresztő bél, D-vitamin-hiány) máig nem szolgálnak kielégítő magyarázattal az epidemiológiai észlelések többségére (például földrajzi régiónként jelentősen eltérő incidenciaértékek, geográfiai "forrópontok", az új esetek megjelenésének szezonális ingadozása, az incidenciacsúcsok ciklicitása). Összefoglalónk célja a gyermekkori 1-es típusú diabetes epidemiológiájára vonatkozó aktuális adatok és háttérelméletek áttekintése. Orv Hetil. 2021; 162(1): 13-22. Summary. According to the latest report of the IDF (International Diabetes Federation), more than 600 000 children under the age of 15 years are living with type 1 diabetes in the world and the number of new cases is estimated to be 98 200 annually. In recent decades, a significant increase in the incidence has been observed globally: during 1989-2013, the annual rate of increase was 3.4% in Europe, suggesting a doubling in the number of patients within approximately 20 years on the continent. The wide variation in incidence has been well documented by epidemiological studies and influenced by geographical and climatic conditions, ethnic and demographic factors. Although the genetic background is the primary risk factor for beta-cell autoimmunity, such dynamic changes in incidence are more likely to be associated with the higher environmental pressure than the increase in genetic load at population level. Environmental factors can also contribute to the pathogenesis of type 1 diabetes as accelerators, causal or protective factors, moreover may even be involved at several points and with several mechanisms at the same time. However, despite the extensive international research on environmental factors, the most popular hypotheses associated with them (e.g., virus infections, hygiene hypothesis, intestinal microbiota, leaky gut, lack of vitamin D) have not yet provided a satisfactory explanation for most epidemiological observations (e.g., geographically significant variability of incidence rates, geographical "hotspots", seasonal fluctuations in new cases, cyclical trends of incidence peaks). In this article, recent data and hypotheses about the epidemiology of childhood type 1 diabetes are summarized. Orv Hetil. 2021; 162(1): 13-22.
Published:
January 3, 2021
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