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Title:

Healthy cardiovascular biomarkers across the lifespan in wild-born chimpanzees ( <i>Pan troglodytes</i> )

Authors:

Cole, Megan F.; Cantwell, Averill; Rukundo, Joshua; Ajarova, Lilly; Fernandez-Navarro, Sofia; Atencia, Rebeca; Rosati, Alexandra G.

Abstract:

Chimpanzees ( Pan troglodytes ) are a crucial model for understanding the evolution of human health and longevity. Cardiovascular disease is a major source of mortality during ageing in humans and therefore a key issue for comparative research. Current data indicate that compared to humans, chimpanzees have proatherogenic blood lipid profiles, an important risk factor for cardiovascular disease in humans. However, most work to date on chimpanzee lipids come from laboratory-living populations where lifestyles diverge from a wild context. Here, we examined cardiovascular profiles in chimpanzees living in African sanctuaries, who range semi-free in large forested enclosures, consume a naturalistic diet, and generally experience conditions more similar to a wild chimpanzee lifestyle. We measured blood lipids, body weight and body fat in 75 sanctuary chimpanzees and compared them to publicly available data from laboratory-living chimpanzees from the Primate Aging Database. We found that semi-free-ranging chimpanzees exhibited lower body weight and lower levels of lipids that are risk factors for human cardiovascular disease, and that some of these disparities increased with age. Our findings support the hypothesis that lifestyle can shape health indices in chimpanzees, similar to effects observed across human populations, and contribute to an emerging understanding of human cardiovascular health in an evolutionary context. This article is part of the theme issue ‘Evolution of the primate ageing process’.

Published:

November 9, 2020

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Title:

Meet the Meat Alternatives: The Value of Alternative Protein Sources

Authors:

Thavamani, Aravind; Sferra, Thomas J.; Sankararaman, Senthilkumar

Abstract:

PURPOSE OF REVIEW: Meat alternatives are non-animal-based proteins with chemical characteristics and aesthetic qualities comparable to meat. The global increase in meat consumption is associated with the adverse environmental impacts such as increased greenhouse gas emissions contributing to global warming and higher water/land use. In this review, we focus on the development, availability, and nutritional value of various meat alternatives and their impact on meat consumption. RECENT FINDINGS: Changing dietary patterns and drive for environmental conservation contribute to the recent increase in the consumption of environmental friendly sources of proteins such as plant-based and mycoprotein-based meat alternatives. Perceived lack of naturalness and poor cultural acceptance present as roadblocks for widespread societal acceptance for meat alternatives. Continued research and efforts are needed to make the meat alternatives more aesthetically appealing with improved nutritive value.

Published:

November 5, 2020

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Title:

Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines

Authors:

Smith, Sarah A.; Ogawa, Sayaka A.; Chau, Lillian; Whelan, Kelly A.; Hamilton, Kathryn E.; Chen, Jie; Tan, Lu; Chen, Eric Z.; Keilbaugh, Sue; Fogt, Franz; Bewtra, Meenakshi; Braun, Jonathan; Xavier, Ramnik J.; Clish, Clary B.; Slaff, Barry; Weljie, Aalim M.; Bushman, Frederic D.; Lewis, James D.; Li, Hongzhe; Master, Stephen R.; Bennett, Michael J.; Nakagawa, Hiroshi; Wu, Gary D.

Abstract:

As the interface between the gut microbiota and the mucosal immune system, there has been great interest in the maintenance of colonic epithelial integrity through mitochondrial oxidation of butyrate, a short-chain fatty acid produced by the gut microbiota. Herein, we showed that the intestinal epithelium can also oxidize long-chain fatty acids, and that luminally-delivered acylcarnitines in bile can be consumed via apical absorption by the intestinal epithelium resulting in mitochondrial oxidation. Finally, intestinal inflammation led to mitochondrial dysfunction in the apical domain of the surface epithelium that may reduce the consumption of fatty acids, contributing to higher concentrations of fecal acylcarnitines in murine Citrobacter rodentium-induced colitis and human inflammatory bowel disease. These results emphasized the importance of both the gut microbiota and the liver in the delivery of energy substrates for mitochondrial metabolism by the intestinal epithelium.

Published:

November 3, 2020

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Title:

Adipose tissue growth and development: the modulating role of ambient temperature

Authors:

Symonds, Michael E.; Pope, Mark; Bloor, Ian; Law, James; Alagal, Reham; Budge, Helen

Abstract:

Adipose tissue is usually laid down in small amounts in the fetus and is characterised as possessing small amounts of the brown adipose tissue specific mitochondrial uncoupling protein 1 (UCP1). In adults, a primary factor determining the abundance and function of UCP1 is ambient temperature. Cold exposure causes activation and the rapid generation of heat through the free flow of protons across the mitochondria with no requirement to convert ADP to ATP. In rodents, housing at an ambient temperature below thermoneutrality promotes the appearance of beige like adipocytes. These arise as discrete regions of UCP1 containing cells in white fat depots. There is increasing evidence to show that, to gain credible translational results on brown and beige fat function in rodent models, they should be housed at thermoneutrality. This not only reflects the type of environment in which humans spend the majority of their time, but is in accord with the rise of global temperature caused by industrialisation and the uncontrolled burning of fossil fuels. There is now good evidence that stimulating brown fat in adult humans by nutritional or pharmacological interventions can improve glucose homeostasis. The challenge, therefore, is to establish credible developmental models in animals maintained at thermoneutrality which will elucidate the true impact of nutrition. The primary focus should fall specifically on the components of breast milk and how these modulate long term effects on brown or beige fat development and function.

Published:

November 1, 2020

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Title:

Reversal of diabetic tractional retinal detachment attributed to keto diet

Authors:

Chandrasekaran, Priya; Rani, Padmaja Kumari

Abstract:

A 40-year-old woman, known type 2 diabetes mellitus, obese (100 kg), on insulin (80 units), was under treatment for unstable proliferative diabetic retinopathy with extramacular tractional retinal detachment (TRD) in the left eye. At 1-year follow-up, she developed progression of TRD involving the macula in the left eye for which she was advised surgery. She did not follow-up for 6 months during which time she had adopted a coconut oil-rich ketogenic diet. She reported losing 25 kg body weight along with reversal of diabetes (Glycosylated Haemglobin (HbA1C) of 5.3% without insulin) in the interim. During this 2-year follow-up visit, it was found that there was complete resolution of macular detachment due to TRD in the left eye with stable vision. This was attributed to the impactful ketogenic diet.

Published:

October 31, 2020

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Title:

High uric acid promotes dysfunction in pancreatic β cells by blocking IRS2/AKT signallingsignalling

Authors:

Hu, Yaqiu; Zhao, Hairong; Lu, Jiaming; Xie, De; Wang, Qiang; Huang, Tianliang; Xin, Hancheng; Hisatome, Ichiro; Yamamoto, Tetsuya; Wang, Wei; Cheng, Jidong

Abstract:

Hyperuricaemia is a disorder of purine metabolism. Elevated serum uric acid is strongly associated with many diseases, including gout, abdominal obesity, insulin resistance, and cardiovascular and kidney disease. Our previous studies showed that high uric acid (HUA) induced insulin resistance in several peripheral organs, including the liver, myocardium and adipose tissue. However, whether HUA directly induces insulin resistance of pancreatic β cells, the only source of insulin in the body and also a sensitive insulin target, is unknown. In this study, pancreatic β cells pretreated with HUA showed impaired insulin expression/secretion, glucose uptake and the glycolytic pathway. RNA-seq revealed that HUA affected the biological processes of INS-1 cells broadly, including oxidoreduction coenzyme metabolic process, pyruvate metabolic process, and glycolytic process. In addition, HUA reduced mitochondrial membrane potential and increased the production of reactive oxygen species(ROS) in INS-1 cells.INS-1 cells pretreated with probenecid, an organic anion transporter inhibitor, protected INS-1 cells against HUA-induced insulin secretion decrease, Pretreatment with N-acetyl-L-cysteine(NAC), a globally used antioxidant, recovered HUA-decreased insulin secretion and glucose uptake by pancreatic β cells. Insulin-like growth factor 1 (IGF-1), the phosphatidylinositol 3-kinase (PI3K) activator, rescues HUA-decreased insulin secretion by re-activating AKT phosphorylation. Thus, HUA induce insulin resistance, impaired insulin secretion and glycolytic pathway of pancreatic ꞵ cell through ROS/AKT/IRS2 pathway.

Published:

October 27, 2020

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Title:

Fatty acid composition and oxidation in beef muscles as affected by ageing times and cooking methods

Authors:

Gruffat, Dominique; Bauchart, Dominique; Thomas, Agnès; Parafita, Emilie; Durand, Denys

Abstract:

This study aimed to determine how ageing and cooking, each one applied to the beef meat most suitable (pan-fried or grilled ribeye steak, braised chuck and fried or roasted rump steak), induce changes in lipid content, fatty acid (FA) composition and lipid oxidation of muscles from 16 cattle representative of animals raised for France meat production. The fattiest muscle (ribeye) was the richest in saturated and monounsaturated FA leading to poor nutritional indexes. In contrast, the leanest muscle (rump) had the highest proportion of polyunsaturated FA and the highest levels of peroxidation without exceeding critical limits. The impact of cooking methods seemed mainly linked to the moisture loss increasing meat fat content and the culinary fat addition whose FA composition marked the meat. Cooking methods induced oxidation phenomena that could exceed the limit thresholds. In conclusion, short cooking time of rump steak was the best combination to meet nutritional expectations.

Published:

October 26, 2020

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Title:

Mitochondrial pyruvate carriers are required for myocardial stress adaptation

Authors:

Zhang, Yuan; Taufalele, Paul V.; Cochran, Jesse D.; Robillard-Frayne, Isabelle; Marx, Jonas Maximilian; Soto, Jamie; Rauckhorst, Adam J.; Tayyari, Fariba; Pewa, Alvin D.; Gray, Lawrence R.; Teesch, Lynn M.; Puchalska, Patrycja; Funari, Trevor R.; McGlauflin, Rose; Zimmerman, Kathy; Kutschke, William J.; Cassier, Thomas; Hitchcock, Shannon; Lin, Kevin; Kato, Kevin M.; Stueve, Jennifer L.; Haff, Lauren; Weiss, Robert M.; Cox, James E.; Rutter, Jared; Taylor, Eric B.; Crawford, Peter A.; Lewandowski, E. Douglas; Des Rosiers, Christine; Abel, E. Dale

Abstract:

Published:

October 26, 2020

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Title:

Mitochondrial pyruvate carriers are required for myocardial stress adaptation

Authors:

Zhang, Yuan; Taufalele, Paul V.; Cochran, Jesse D.; Robillard-Frayne, Isabelle; Marx, Jonas Maximilian; Soto, Jamie; Rauckhorst, Adam J.; Tayyari, Fariba; Pewa, Alvin D.; Gray, Lawrence R.; Teesch, Lynn M.; Puchalska, Patrycja; Funari, Trevor R.; McGlauflin, Rose; Zimmerman, Kathy; Kutschke, William J.; Cassier, Thomas; Hitchcock, Shannon; Lin, Kevin; Kato, Kevin M.; Stueve, Jennifer L.; Haff, Lauren; Weiss, Robert M.; Cox, James E.; Rutter, Jared; Taylor, Eric B.; Crawford, Peter A.; Lewandowski, E. Douglas; Des Rosiers, Christine; Abel, E. Dale

Abstract:

In addition to fatty acids, glucose and lactate are important myocardial substrates under physiologic and stress conditions. They are metabolized to pyruvate, which enters mitochondria via the mitochondrial pyruvate carrier (MPC) for citric acid cycle metabolism. In the present study, we show that MPC-mediated mitochondrial pyruvate utilization is essential for the partitioning of glucose-derived cytosolic metabolic intermediates, which modulate myocardial stress adaptation. Mice with cardiomyocyte-restricted deletion of subunit 1 of MPC (cMPC1−/−) developed age-dependent pathologic cardiac hypertrophy, transitioning to a dilated cardiomyopathy and premature death. Hypertrophied hearts accumulated lactate, pyruvate and glycogen, and displayed increased protein O-linked N-acetylglucosamine, which was prevented by increasing availability of non-glucose substrates in vivo by a ketogenic diet (KD) or a high-fat diet, which reversed the structural, metabolic and functional remodelling of non-stressed cMPC1−/− hearts. Although concurrent short-term KDs did not rescue cMPC1−/− hearts from rapid decompensation and early mortality after pressure overload, 3 weeks of a KD before transverse aortic constriction was sufficient to rescue this phenotype. Together, our results highlight the centrality of pyruvate metabolism to myocardial metabolism and function.

Published:

October 26, 2020

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Title:

Nutritional modulation of heart failure in mitochondrial pyruvate carrier–deficient mice

Authors:

McCommis, Kyle S.; Kovacs, Attila; Weinheimer, Carla J.; Shew, Trevor M.; Koves, Timothy R.; Ilkayeva, Olga R.; Kamm, Dakota R.; Pyles, Kelly D.; King, M. Todd; Veech, Richard L.; DeBosch, Brian J.; Muoio, Deborah M.; Gross, Richard W.; Finck, Brian N.

Abstract:

The myocardium is metabolically flexible; however, impaired flexibility is associated with cardiac dysfunction in conditions including diabetes and heart failure. The mitochondrial pyruvate carrier (MPC) complex, composed of MPC1 and MPC2, is required for pyruvate import into the mitochondria. Here we show that MPC1 and MPC2 expression is downregulated in failing human and mouse hearts. Mice with cardiac-specific deletion of Mpc2 (CS-MPC2−/−) exhibited normal cardiac size and function at 6 weeks old, but progressively developed cardiac dilation and contractile dysfunction, which was completely reversed by a high-fat, low-carbohydrate ketogenic diet. Diets with higher fat content, but enough carbohydrate to limit ketosis, also improved heart failure, while direct ketone body provisioning provided only minor improvements in cardiac remodelling in CS-MPC2−/− mice. An acute fast also improved cardiac remodelling. Together, our results reveal a critical role for mitochondrial pyruvate use in cardiac function, and highlight the potential of dietary interventions to enhance cardiac fat metabolism to prevent or reverse cardiac dysfunction and remodelling in the setting of MPC deficiency.

Published:

October 26, 2020

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Title:

Medial Injury/Dysfunction Induced Granulation Tissue Repair is the Pathogenesis of Atherosclerosis

Authors:

Wang, Xinggang; Sun, Aijun; Ge, Junbo

Abstract:

Atherosclerosis, a chronic lesion of vascular wall, remains a leading cause of death and loss of life years. Classical hypotheses for atherosclerosis are long-standing mainly to explain atherogenesis. Unfortunately, these hypotheses may not explain the variation in the susceptibility to atherosclerosis. These issues are controversial over the past 150 years. Atherosclerosis from human coronary arteries was examined and triangle of media was found to be a true portraiture of cells injury in the media, and triangle of intima was a true portraiture of myofibroblast proliferation, extracellular matrix (ECM) secretion, collagen fiber formation and intimal thickening to repair media dysfunction. Myofibroblasts, ECM and lumen (intima)/vasa vasorum (VV) (adventitia) constitute granulation tissue repair. With granulation tissue hyperplasia, lots of collagen fibers (normal or denatured), foam cells and new capillaries formed. Thus, the following theory was postulated: Risk factors induce smooth muscle cells (SMCs) injury/loss, and fibrosis or structure destruction could be developed in the media, which lead to media dysfunction. Media dysfunction prompts disturbed mechanical properties of blood vessels, resulting in bigger pressure buildup in the intima and adventitia. Granulation tissues in the intima/adventitia develop to repair the injured media. Atherosclerosis, stiffening or aneurysm develops depending on media dysfunction severity and granulated tissue repair mode/degree. Nearly all characteristics of clinical atherosclerosis could be ideally interpreted with the theory. We believe that media dysfunction is a key initiator in the pathogenesis of atherosclerosis. It is expected that media dysfunction theory of atherosclerosis, should offer better understanding of the etiology for atherosclerosis.

Published:

October 21, 2020

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Title:

Novel approach to quantify mitochondrial content and intrinsic bioenergetic efficiency across organs

Authors:

McLaughlin, Kelsey L.; Hagen, James T.; Coalson, Hannah S.; Nelson, Margaret A. M.; Kew, Kimberly A.; Wooten, Ashley R.; Fisher-Wellman, Kelsey H.

Abstract:

Human disease pathophysiology commonly involves metabolic disruption at both the cellular and subcellular levels. Isolated mitochondria are a powerful model for separating global cellular changes from intrinsic mitochondrial alterations. However, common laboratory practices for isolating mitochondria (e.g., differential centrifugation) routinely results in organelle preparations with variable mitochondrial purity. To overcome this issue, we developed a mass spectrometry-based method that quantitatively evaluates sample-specific percent mitochondrial enrichment. Sample-specific mitochondrial enrichment was then used to correct various biochemical readouts of mitochondrial function to a ‘fixed’ amount of mitochondrial protein, thus allowing for intrinsic mitochondrial bioenergetics, relative to the underlying proteome, to be assessed across multiple mouse tissues (e.g., heart, brown adipose, kidney, liver). Our results support the use of mitochondrial-targeted nLC-MS/MS as a method to quantitate mitochondrial enrichment on a per-sample basis, allowing for unbiased comparison of functional parameters between populations of mitochondria isolated from metabolically distinct tissues. This method can easily be applied across multiple experimental settings in which intrinsic shifts in the mitochondrial network are suspected of driving a given physiological or pathophysiological outcome.

Published:

October 19, 2020

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Title:

Arachidonic acid metabolism controls macrophage alternative activation through regulating oxidative phosphorylation in PPARG dependent manner

Authors:

Xu, Miao; Wang, Xiaohong; Jia, Xudong; Li, Yongning; Geng, Xue; Zhang, Lishi; Yang, Hui

Abstract:

Macrophages polarization is mainly controlled by metabolic reprogramming in microenvironment, thus leading to distinct outcomes of various diseases. However, the role of lipid metabolism in the regulation of macrophage alternative activation is incompletely understood. Using human THP-1 and mouse bone marrow derived macrophages polarization models, we revealed a pivotal role for arachidonic acid metabolism in controlling the polarization of M1 and M2 macrophages. We demonstrated that M2 macrophage polarization was inhibited by arachidonic acid, but inversely facilitated by its derived metabolite prostaglandin E2 (PGE2). Furthermore, PPARG bridges these two unconnected processes via modulating oxidative phosphorylation. These results highlight the critical role of arachidonic acid metabolism as an immune regulator in modulating metabolic homeostasis and pathological process.

Published:

October 15, 2020

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Title:

glycated hemoglobin level as a predictor of severity of coronary artery disease in non diabetic patients

Authors:

Mirza*, Aram J.; Mohammad, Hemn H.; Jaefer, Farman; Singh, Jagdeep; Lang, Chim C.

Abstract:

International Journal of Diabetes and Treatment is a high quality open access journal and discusses the diagnosis, treatment or control of diabetes, which is a disease caused by a problem in the production of insulin in the human body, which leads to a number of problems with the functioning of the body.

Published:

October 15, 2020

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Title:

Ketogenic diet: a tool for the management of neuroendocrine neoplasms?

Authors:

Muscogiuri, Giovanna; Barrea, Luigi; Campolo, Federica; Sbardella, Emilia; Sciammarella, Concetta; Tarsitano, Maria Grazia; Bottiglieri, Filomena; Colao, Annamaria; Faggiano, Antongiulio

Abstract:

Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms, whose incidence has rapidly increased in the last years. Nutrition plays an important role in their management; indeed, malnutrition negatively impacts on rates of complications, hospitalization, hospital stay, costs and mortality. Furthermore, it has been reported that a poor nutritional status could influence the outcome of patients with pancreatic NENs. Moreover, obesity, predisposing to insulin resistance and compensatory hyperinsulinemia, could stimulate the growth of these neoplasms. Ketogenic diet (KD), a high-fat, low-carbohydrate diet with adequate amounts of protein, has been reported to be a promising approach for the management of several types of cancer, mostly gynecological and neurological ones. Indeed, it appears to sensitize most cancers to standard treatment by exploiting the reprogramed metabolism of cancer cells and thus resulting in a promising candidate as an adjuvant cancer therapy. Thus, the aim of this review is to provide an overview on the importance of nutrition in cancer management and in particular in NENs' setting. Furthermore, we reported the current evidence on the efficacy of KD in the management of cancer and based on molecular mechanisms; we also hypothesize the potential use of this nutritional pattern in the management of NENs.

Published:

October 14, 2020

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Title:

High-refined carbohydrate diet leads to polycystic ovary syndrome-like features and reduced ovarian reserve in female rats

Authors:

Niño, Oscar M. S.; da Costa, Charles S.; Torres, Karine M.; Zanol, Jordana F.; Freitas-Lima, Leandro C.; Miranda-Alves, Leandro; Graceli, Jones B.

Abstract:

Obesity is associated with several female reproductive complications, such as polycystic ovary syndrome (PCOS). The exact mechanism of this relationship remains unclear. Few previous studies using diet containing refined carbohydrate (HCD) leading to obesity have been performed and it is unclear if HCD is linked with reproductive dysfunctions. In this investigation, we assessed whether subchronic HCD exposure results in reproductive and other irregularities. Female rats were fed with HCD for 15 days and metabolic outcomes and reproductive tract morphophysiology were assessed. We further assessed reproductive tract inflammation, oxidative stress (OS) and fibrosis. HCD rats displayed metabolic impairments, such as an increase in body weight/adiposity, adipocyte hypertrophic, abnormal lipid profile, glucose tolerance and insulin resistance (IR) and hyperleptinemia. Improper functioning of the HCD reproductive tract was observed. Specifically, irregular estrous cyclicity, high LH levels and abnormal ovarian morphology coupled with reduction in primordial and primary follicle numbers was observed, suggesting ovarian reserve depletion. Improper follicular development and a reduction in antral follicles, corpora lutea and granulosa layer area together with an increase in cystic follicles were apparent. Uterine atrophy and reduction in endometrial gland (GE) number was observed in HCD rats. Reproductive tract inflammation, OS and fibrosis were seen in HCD rats. Further, strong positive correlations were observed between body weight/adiposity and IR with estrous cycle length, cystic follicles, ovarian reserve, GE and other abnormalities. Thus, these data suggest that the subchronic HCD exposure led to PCOS-like features, impaired ovarian reserve, GE number, and other reproductive abnormalities in female rats.

Published:

October 10, 2020

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Title:

Impossible to go Beyond Beef? A Nutriomics Comparison

Authors:

van Vliet, Stephan; Bain, James; Muehlbauer, Michael; Provenza, Frederick; Kronberg, Scott; Pieper, Carl; Huffman, Kim; Kraus, William

Abstract:

Abstract Concerns regarding the effects of red meat on human and environmental health are prompting consumer interest in plant-based diets. As global food systems strive to meet the dietary needs of an estimated mid-century population of 10 billion, a new generation of plant-based meat alternatives—formulated to mimic the taste and nutritional composition of red meat—have attracted considerable consumer interest, research attention, and media coverage. We used untargeted metabolomics to provide an in-depth comparison of the nutrient profiles of grass-fed ground beef and a market-leading plant-based meat alternative. Metabolomics revealed a 90% difference in nutritional profiles beef and a popular plant-based meat, many of which can have important consumer health implications. This information could not be determined from their Nutrition Facts, which suggests nutritional similarity. Our findings indicate that beef and a popular plant-based meat should not be viewed as nutritionally interchangeable, but as complementary in terms of provided nutritional entities. As society aims to increase food production with ~ 60% by 2050, the meat and the plant-based meat industries will likely coexist and have to complement each other in order this reach this goal.

Published:

October 9, 2020

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Title:

The Nutrivore: Low Carbohydrate Diets and Health (An Independent Meta-Analysis of Intervention Trials)

Authors:

​

Abstract:

Published:

October 8, 2020

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Title:

Environmental drivers of megafauna and hominin extinction in Southeast Asia

Authors:

Louys, Julien; Roberts, Patrick

Abstract:

Published:

October 7, 2020

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Title:

Medical Management of Advanced Oxalate Nephropathy Secondary to Gastric Bypass Surgery

Authors:

Kamel, Tony H.; Maroz, Natallia

Abstract:

A 73-year-old Caucasian female with a history of obesity status post Roux-en-Y gastric bypass (RYGB) surgery presented with generalized weakness and was found to have acute kidney injury (AKI) with a creatinine peak of 9.1 mg/dL above her baseline of 1.2 mg/dL, and anemia with hemoglobin 5.7 g/dl. Kidney biopsy revealed oxalate nephropathy likely related to gastric bypass surgery four years prior. RYGB is a strong risk factor for hyperoxaluria, nephrolithiasis, and oxalate nephropathy which often progresses to end-stage renal disease (ESRD). Meaningful treatment strategies for this disease entity are lacking. We present a case in which dietary and pharmacological management without the use of renal replacement therapy resulted in stabilization of chronic kidney disease (CKD) stage 5 for seven years at the time of this writing.

Published:

October 7, 2020

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Title:

Medical Management of Advanced Oxalate Nephropathy Secondary to Gastric Bypass Surgery

Authors:

Kamel, Tony H.; Maroz, Natallia

Abstract:

Abstract

A 73-year-old Caucasian female with a history of obesity status post Roux-en-Y gastric bypass (RYGB) surgery presented with generalized weakness and was found to have acute kidney injury (AKI) with a creatinine peak of 9.1 mg/dL above her baseline of 1.2 mg/dL, and anemia with hemoglobin 5.7 g/dl. Kidney biopsy revealed oxalate nephropathy likely related to gastric bypass surgery four years prior. RYGB is a strong risk factor for hyperoxaluria, nephrolithiasis, and oxalate nephropathy which often progresses to end-stage renal disease (ESRD). Meaningful treatment strategies for this disease entity are lacking. We present a case in which dietary and pharmacological management without the use of renal replacement therapy resulted in stabilization of chronic kidney disease (CKD) stage 5 for seven years at the time of this writing.

Published:

October 6, 2020

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Title:

Effect of a 90 g/day low-carbohydrate diet on glycaemic control, small, dense low-density lipoprotein and carotid intima-media thickness in type 2 diabetic patients: An 18-month randomised controlled trial

Authors:

Chen, Chin-Ying; Huang, Wei-Sheng; Chen, Hui-Chuen; Chang, Chin-Hao; Lee, Long-Teng; Chen, Heng-Shuen; Kang, Yow-Der; Chie, Wei-Chu; Jan, Chyi-Feng; Wang, Wei-Dean; Tsai, Jaw-Shiun

Abstract:

Aim This study explored the effect of a moderate (90 g/d) low-carbohydrate diet (LCD) in type 2 diabetes patients over 18 months. Methods Ninety-two poorly controlled type 2 diabetes patients aged 20–80 years with HbA1c ≥7.5% (58 mmol/mol) in the previous three months were randomly assigned to a 90 g/d LCD r traditional diabetic diet (TDD). The primary outcomes were glycaemic control status and change in medication effect score (MES). The secondary outcomes were lipid profiles, small, dense low-density lipoprotein (sdLDL), serum creatinine, microalbuminuria and carotid intima-media thickness (IMT). Results A total of 85 (92.4%) patients completed 18 months of the trial. At the end of the study, the LCD and TDD group consumed 88.0±29.9 g and 151.1±29.8 g of carbohydrates, respectively (p < 0.05). The 18-month mean change from baseline was statistically significant for the HbA1c (-1.6±0.3 vs. -1.0±0.3%), 2-h glucose (-94.4±20.8 vs. -18.7±25.7 mg/dl), MES (-0.42±0.32 vs. -0.05±0.24), weight (-2.8±1.8 vs. -0.7±0.7 kg), waist circumference (-5.7±2.7 vs. -1.9±1.4 cm), hip circumference (-6.1±1.8 vs. -2.9±1.7 cm) and blood pressure (-8.3±4.6/-5.0±3 vs. 1.6±0.5/2.5±1.6 mmHg) between the LCD and TDD groups (p

Published:

October 5, 2020

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Title:

Effect of a 90 g/day low-carbohydrate diet on glycaemic control, small, dense low-density lipoprotein and carotid intima-media thickness in type 2 diabetic patients: An 18-month randomised controlled trial

Authors:

Chen, Chin-Ying; Huang, Wei-Sheng; Chen, Hui-Chuen; Chang, Chin-Hao; Lee, Long-Teng; Chen, Heng-Shuen; Kang, Yow-Der; Chie, Wei-Chu; Jan, Chyi-Feng; Wang, Wei-Dean; Tsai, Jaw-Shiun

Abstract:

Aim This study explored the effect of a moderate (90 g/d) low-carbohydrate diet (LCD) in type 2 diabetes patients over 18 months. Methods Ninety-two poorly controlled type 2 diabetes patients aged 20–80 years with HbA1c ≥7.5% (58 mmol/mol) in the previous three months were randomly assigned to a 90 g/d LCD r traditional diabetic diet (TDD). The primary outcomes were glycaemic control status and change in medication effect score (MES). The secondary outcomes were lipid profiles, small, dense low-density lipoprotein (sdLDL), serum creatinine, microalbuminuria and carotid intima-media thickness (IMT). Results A total of 85 (92.4%) patients completed 18 months of the trial. At the end of the study, the LCD and TDD group consumed 88.0±29.9 g and 151.1±29.8 g of carbohydrates, respectively (p < 0.05). The 18-month mean change from baseline was statistically significant for the HbA1c (-1.6±0.3 vs. -1.0±0.3%), 2-h glucose (-94.4±20.8 vs. -18.7±25.7 mg/dl), MES (-0.42±0.32 vs. -0.05±0.24), weight (-2.8±1.8 vs. -0.7±0.7 kg), waist circumference (-5.7±2.7 vs. -1.9±1.4 cm), hip circumference (-6.1±1.8 vs. -2.9±1.7 cm) and blood pressure (-8.3±4.6/-5.0±3 vs. 1.6±0.5/2.5±1.6 mmHg) between the LCD and TDD groups (p

Published:

October 5, 2020

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Title:

Fructose and uric acid as drivers of a hyperactive foraging response: A clue to behavioral disorders associated with impulsivity or mania?

Authors:

Johnson, Richard J.; Wilson, William L.; Bland, Sondra T.; Lanaspa, Miguel A.

Abstract:

Several behavioral disorders, including attention deficit hyperactivity disorder (ADHD), bipolar disorder, and aggressive behaviors are linked with sugar intake and obesity. The reason(s) for this association has been unclear. Here we present a hypothesis supporting a role for fructose, a component of sugar and high fructose corn syrup (HFCS), and uric acid (a fructose metabolite), in increasing the risk for these behavioral disorders. Recent studies have shown that the reason fructose intake is strongly associated with development of metabolic syndrome is that fructose intake activates an evolutionary-based survival pathway that stimulates foraging behavior and the storage of energy as fat. While modest intake may aid animals that would like to store fat as a protective response from food shortage or starvation, we propose that high intake of sugar and HFCS causes a hyperactive foraging response that stimulates craving, impulsivity, risk taking and aggression that increases the risk for ADHD, bipolar disease and aggressive behavior. High glycemic carbohydrates and salty foods may also contribute as they can be converted to fructose in the body. Some studies suggest uric acid produced during fructose metabolism may mediate some of these effects. Chronic stimulation of the pathway could lead to desensitization of hedonic responses and induce depression. In conclusion, a hyperactive foraging response driven by high glycemic carbohydrates and sugars may contribute to affective disorders.

Published:

October 1, 2020

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Title:

Myofibroblast Forms Atherosclerotic Plaques

Authors:

Wang, Xinggang; Ge, Junbo

Abstract:

For decades, smooth muscle cells (SMCs) and macrophages are considered as the main contributors to atherosclerotic plaques. However, we found that in the human coronary atherosclerotic plaques, SMCs were few, while lots of myofibroblasts infiltrated in the intima near the lumen (fibrous cap) and their distribution was highly positive related to intimal thickness. In addition to lots of foam cells formation, collagen fibers were forming in the thickening intima near the lumen (fibrous cap), and denaturing or calcifying gradually far from the lumen, which evolved into various complex plaques. In vitro, myofibroblasts could actively take lots of low-density lipoprotein (LDL) to enhance proliferation. Lots of collagen fibers, foam cells and extracellular lipids accumulation emerged in myofibroblasts cultured with 5% FBS high glucose DMEM without adding modified LDL. It is consistent with the characteristics of human coronary atherosclerotic plaques. It is the first time that lipid rich plaques with lots of foam cells, extracellular lipids and collagen fibers formed in vitro. It demonstrated that myofibroblast should be the direct and main source of collagen fibers, foam cells and extracellular lipids. This suggests that atherosclerosis is not as complicated as previously considered, and it might be mainly a process of myofibroblast remodeling to vascular injury caused by various risk factors. This study made the pathogenesis of atherosclerosis clearer. It would provide a target cell for future treatments of atherosclerotic diseases. In vitro atherosclerotic plaques model formed by human myofibroblasts would be an efficient and convenient way to study atherosclerosis.

Published:

September 29, 2020

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Title:

A KETOGENIC DIET COMBINED WITH EXERCISE ALTERS MITOCHONDRIAL FUNCTION IN HUMAN SKELETAL MUSCLE WHILE IMPROVING METABOLIC HEALTH

Authors:

Miller, Vincent J; LaFountain, Richard A; Barnhart, Emily; Sapper, Teyrn S; Short, Jay; Arnold, William David; Hyde, Parker N; Crabtree, Christopher D; Kackley, Madison L; Kraemer, William J.; Villamena, Frederick; Volek, Jeffrey S.

Abstract:

Animal data indicate that ketogenic diets are associated with improved mitochondrial function, but human data are lacking. We aimed to characterize skeletal muscle mitochondrial changes in response to a ketogenic diet combined with exercise training in healthy individuals. Twenty-nine physically active adults completed a 12-week supervised exercise program after self-selection into a ketogenic diet (KD, n=15) group or maintenance of their habitual mixed diet (MD, n=14). Measures of metabolic health and muscle biopsies (Vastus lateralis) were obtained before and after the intervention. Mitochondria were isolated from muscle and studied after exposure to carbohydrate (pyruvate), fat (palmitoyl-L-carnitine), and ketone (β-hydroxybutyrate+acetoacetate) substrates. Compared to MD, the KD resulted in increased whole-body resting fat oxidation (p<0.001) and decreased fasting insulin (p=0.019), insulin resistance (HOMA-IR, p=0.022), and visceral fat (p

Published:

September 28, 2020

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Title:

Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial

Authors:

Lowe, Dylan A.; Wu, Nancy; Rohdin-Bibby, Linnea; Moore, A. Holliston; Kelly, Nisa; Liu, Yong En; Philip, Errol; Vittinghoff, Eric; Heymsfield, Steven B.; Olgin, Jeffrey E.; Shepherd, John A.; Weiss, Ethan J.

Abstract:

Importance

The efficacy and safety of time-restricted eating have not been explored in large randomized clinical trials.

Objective

To determine the effect of 16:8-hour time-restricted eating on weight loss and metabolic risk markers.

Interventions

Participants were randomized such that the consistent meal timing (CMT) group was instructed to eat 3 structured meals per day, and the time-restricted eating (TRE) group was instructed to eatad libitumfrom 12:00pmuntil 8:00pmand completely abstain from caloric intake from 8:00pmuntil 12:00pmthe following day.

Design, Setting, and Participants

This 12-week randomized clinical trial including men and women aged 18 to 64 years with a body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 27 to 43 was conducted on a custom mobile study application. Participants received a Bluetooth scale. Participants lived anywhere in the United States, with a subset of 50 participants living near San Francisco, California, who underwent in-person testing.

Main Outcomes and Measures

The primary outcome was weight loss. Secondary outcomes from the in-person cohort included changes in weight, fat mass, lean mass, fasting insulin, fasting glucose, hemoglobin A1clevels, estimated energy intake, total energy expenditure, and resting energy expenditure.

Results

Overall, 116 participants (mean [SD] age, 46.5 [10.5] years; 70 [60.3%] men) were included in the study. There was a significant decrease in weight in the TRE (−0.94 kg; 95% CI, −1.68 to −0.20;P = .01), but no significant change in the CMT group (−0.68 kg; 95% CI, -1.41 to 0.05,P = .07) or between groups (−0.26 kg; 95% CI, −1.30 to 0.78;P = .63). In the in-person cohort (n = 25 TRE, n = 25 CMT), there was a significant within-group decrease in weight in the TRE group (−1.70 kg; 95% CI, −2.56 to −0.83;P < .001). There was also a significant difference in appendicular lean mass index between groups (−0.16 kg/m2; 95% CI, −0.27 to −0.05;P = .005). There were no significant changes in any of the other secondary outcomes within or between groups. There were no differences in estimated energy intake between groups.

Conclusions and Relevance

Time-restricted eating, in the absence of other interventions, is not more effective in weight loss than eating throughout the day.

Trial Registration

ClinicalTrials.gov Identifiers:NCT03393195andNCT03637855

Published:

September 28, 2020

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Title:

Nutritional Aspects of Spermidine

Authors:

Madeo, Frank; Hofer, Sebastian J.; Pendl, Tobias; Bauer, Maria A.; Eisenberg, Tobias; Carmona-Gutierrez, Didac; Kroemer, Guido

Abstract:

Natural polyamines (spermidine and spermine) are small, positively charged molecules that are ubiquitously found within organisms and cells. They exert numerous (intra)cellular functions and have been implicated to protect against several age-related diseases. Although polyamine levels decline in a complex age-dependent, tissue-, and cell type-specific manner, they are maintained in healthy nonagenarians and centenarians. Increased polyamine levels, including through enhanced dietary intake, have been consistently linked to improved health and reduced overall mortality. In preclinical models, dietary supplementation with spermidine prolongs life span and health span. In this review, we highlight salient aspects of nutritional polyamine intake and summarize the current knowledge of organismal and cellular uptake and distribution of dietary (and gastrointestinal) polyamines and their impact on human health. We further summarize clinical and epidemiological studies of dietary polyamines.

Published:

September 23, 2020

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Title:

Role of a Ketogenic Diet on Body Composition, Physical Health, Psychosocial Well-Being and Sports Performance in Athletes: A Scoping Review

Authors:

Bowler, Amy-Lee; Polman, Remco

Abstract:

BACKGROUND: Recently, a focus has been placed on investigating the potential benefits of adherence to a ketogenic diet in enhancing body composition, physical health, psychological well-being, and performance of athletes from various sporting disciplines. As the available research is yet to be collated and analyzed in a single review, this scoping review aims to analyze and draw conclusions from the available literature that exists on the efficacy of a ketogenic diet among athletic populations. METHODS: Several primary research databases and any relevant citation lists were searched to locate appropriate studies for inclusion in this scoping review. Studies that investigated the effects of adherence to a ketogenic diet (KD), defined by a carbohydrate intake of less than 5% of total energy intake, on body composition, physical health, psychological well-being, and performance among an athletic population were included in the review. From 814 articles screened, 12 were identified as meeting the inclusion criteria and were included in the final scoping review. RESULTS: Adherence to a KD has beneficial effects on body weight and fat mass. Varying effects were identified on physical health with the diet, eliciting positive effects on fat oxidation but potentially deleterious effects on stool microbiota and iron metabolism. Conflicting results were reported regarding the effects of a KD on sporting performance. Benefits were reported regarding athlete well-being following commencement of a KD, but only after week two. CONCLUSIONS: The results of this scoping review demonstrate that there are both beneficial and detrimental effects associated with adherence to a KD among athletic populations. It is understood that further research is required to make any concrete recommendations regarding a KD to athletes.

Published:

September 23, 2020

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Title:

β-Hydroxybutyrate inhibits inflammasome activation to attenuate Alzheimer's disease pathology

Authors:

Shippy, Daniel; Wilhelm, Connor; Viharkumar, Patel; Raife, Thomas; Ulland, Tyler

Abstract:

Alzheimer’s disease (AD) is a progressive, late-onset dementia with no effective treatment available. Recent studies suggest that AD pathology is driven by age-related changes in metabolism. Alterations in metabolism, such as placing patients on a ketogenic diet, can alter cognition by an unknown mechanism. One of the ketone bodies produced as a result of ketogenesis, β-hydroxybutyrate (BHB), is known to inhibit NLRP3 inflammasome activation. Therefore, we tested if BHB inhibition of the NLRP3 inflammasome reduces overall AD pathology in the 5XFAD mouse model of AD. Here, we find BHB levels are lower in red blood cells and brain parenchyma of AD patients when compared with non-AD controls. Furthermore, exogenous BHB administration reduced plaque formation, microgliosis, apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) speck formation, and caspase-1 activation in the 5XFAD mouse model of AD. Taken together, our findings demonstrate that BHB reduces AD pathology by inhibiting NLRP3 inflammasome activation. Additionally, our data suggest dietary or pharmacological approaches to increase BHB levels as promising therapeutic strategies for AD.

Published:

September 21, 2020

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Title:

Dietary Fructose Alters the Composition, Localization and Metabolism of Gut Microbiota in Association with Worsening Colitis

Authors:

Montrose, David C.; Nishiguchi, Ryohei; Basu, Srijani; Staab, Hannah A.; Zhou, Xi Kathy; Wang, Hanhan; Meng, Lingsong; Johncilla, Melanie; Cubillos-Ruiz, Juan R.; Morales, Diana K.; Wells, Martin T.; Simpson, Kenneth W.; Zhang, Shiying; Dogan, Belgin; Jiao, Chen; Fei, Zhangjun; Oka, Akihiko; Herzog, Jeremy W.; Sartor, R. Balfour; Dannenberg, Andrew J.

Abstract:

Abstract

Background & Aims

The incidence of inflammatory bowel diseases has increased over the last half century, suggesting a role for dietary factors. Fructose consumption has increased in recent years. Recently, a high fructose diet (HFrD) was shown to enhance DSS-induced colitis in mice. The primary objectives of the current study were to elucidate the mechanism(s) underlying the pro-colitic effects of dietary fructose and to determine whether this effect occurs in both microbially-driven and genetic models of colitis.

Methods

Antibiotics and germ-free mice were used to determine the relevance of microbes for HFrD-induced worsening of colitis. Mucus thickness and quality were determined by histological analyses. 16S rRNA profiling, in situ hybridization, metatranscriptomic analyses and fecal metabolomics were used to determine microbial composition, spatial distribution and metabolism. The significance of a HFrD on pathogen and genetic-driven models of colitis was determined using Citrobacter rodentium infection and Il10-/- mice, respectively.

Results

Reducing or eliminating bacteria attenuated HFrD-mediated worsening of DSS-induced colitis. HFrD feeding enhanced access of gut luminal microbes to the colonic mucosa by reducing thickness and altering the quality of colonic mucus. Feeding a HFrD also altered gut microbial populations and metabolism including reduced protective commensal and bile salt hydrolase-expressing microbes, and increased luminal conjugated bile acids. Administration of conjugated bile acids to mice worsened DSS-induced colitis. The HFrD also worsened colitis in Il10-/- mice and mice infected with C. rodentium.

Conclusions

Excess dietary fructose consumption has a pro-colitic effect that can be explained by changes in the composition, distribution and metabolic function of resident enteric microbiota.

Published:

September 19, 2020

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Title:

Intake and metabolism of omega-3 and omega-6 polyunsaturated fatty acids: nutritional implications for cardiometabolic diseases

Authors:

Schulze, Matthias B.; Minihane, Anne Marie; Saleh, Rasha Noureldin M.; Risérus, Ulf

Abstract:

Summary

Prospective observational studies support the use of long-chain omega-3 polyunsaturated fatty acids (PUFAs) in the primary prevention of atherosclerotic cardiovascular disease; however, randomised controlled trials, have often reported neutral findings. There is a long history of debate about the potential harmful effects of a high intake of omega-6 PUFAs, although this idea is not supported by prospective observational studies or randomised controlled trials. Health effects of PUFAs might be influenced by Δ-5 and Δ-6 desaturases, the key enzymes in the metabolism of PUFAs. The activity of these enzymes and modulation by variants in encoding genes (FADS1-2-3 gene cluster) are linked to several cardiometabolic traits. This Review will further consider non-genetic determinants of desaturase activity, which have the potential to modify the availability of PUFAs to tissues. Finally, we discuss the consequences of altered desaturase activity in the context of PUFA intake, that is, gene–diet interactions and their clinical and public health implications.

Published:

September 16, 2020

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Title:

Circulating plasma fatty acids and risk of pancreatic cancer: results from the Golestan Cohort Study

Authors:

Shishavan, Neda Ghamarzad; Mohamadkhani, Ashraf; Sepanlou, Sadaf Ghajarieh; Masoudi, Sahar; Sharafkhah, Maryam; Poustchi, Hossein; Hekmatdoost, Azita; Pourshams, Akram

Abstract:

Summary

Background & Aims

Pancreatic cancer (PC) with a dismal prognosis is considered as a fatal malignancy, attracting the scientists' attention to study its causes and pathogenesis pathways. Given the lack of enough evidence and conflicting findings about the association of PC risk with plasma fatty acids, we aimed to explore the associations of circulating plasma fatty acids with the risk of PC in a cohort study.

Methods

From about 50,000 subjects participated in this cohort study in 2004–2008, fifty incident cases of PC were recruited and 150 controls matched by age, sex and residence place (urban/rural) were randomly selected. The plasma fatty acids composition was measured by gas chromatography with Flame Ionization Detector (GC-FID) in plasma samples collected at the baseline of cohort study. Multivariable conditional logistic regression was used to estimate OR (with 95% CI) of PC risk associated with plasma levels of fatty acids considering known potential risk factors for PC.

Results

Our findings showed that total saturated fatty acids and total industrial trans fats were not associated with the risk of PC; whereas, statistically significant inverse associations were found between high plasma levels of total mono-unsaturated fatty acids (MUFAs), omega-3 and ruminant trans fatty acids with the risk of PC [ORQ1-Q4=0.31 (0.11-0.89), OR Q2-Q1=0.30 (0.10-0.91) and ORQ2-Q1 =0.15 (0.04-0.49), respectively]. Omega-6 fatty acids especially high plasma levels of Arachidonic acid was positively associated with the risk of PC [ORQ1-Q3=11.07 (3.50-35.02)].

Conclusion

Except for the plasma circulating whole fats, the levels of different classes of fats may significantly change pancreatic cancer susceptibility. Unsaturated fatty acids including omega-3-PUFA and MUFA are considered as protective biomarkers in PC prevention. On the contrary, omega-6-fatty acids are positively associated with the risk of PC.

Published:

September 15, 2020

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Title:

Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model

Authors:

Ryu, Seungjin; Shchukina, Irina; Youm, Yun-Hee; Qing, Hua; Hilliard, Brandon K.; Dlugos, Tamara; Zhang, Xinbo; Yasumoto, Yuki; Booth, Carmen J.; Fernández-Hernando, Carlos; Suárez, Yajaira; Khanna, Kamal M.; Horvath, Tamas L.; Dietrich, Marcelo O.; Artyomov, Maxim N.; Wang, Andrew; Dixit, Vishwa Deep

Abstract:

Increasing age is the strongest predictor of risk of COVID-19 severity. Unregulated cytokine storm together with impaired immunometabolic response leads to highest mortality in elderly infected with SARS-CoV-2. To investigate how aging compromises defense against COVID-19, we developed a model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain MHV-A59 (mCoV-A59) that recapitulated majority of clinical hallmarks of COVID-19. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Ketogenic diet increases beta-hydroxybutyrate, expands tissue protective γδ T cells, deactivates the inflammasome and decreases pathogenic monocytes in lungs of infected aged mice. These data underscore the value of mCoV-A59 model to test mechanism and establishes harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against COVID-19 in the elderly. Highlights: - Natural MHV-A59 mouse coronavirus infection mimics COVID-19 in elderly.- Aged infected mice have systemic inflammation and inflammasome activation.- Murine beta coronavirus (mCoV) infection results in loss of pulmonary γδ T cells.- Ketones protect aged mice from infection by reducing inflammation. eTOC Blurb: Elderly have the greatest risk of death from COVID-19. Here, Ryu et al report an aging mouse model of coronavirus infection that recapitulates clinical hallmarks of COVID-19 seen in elderly. The increased severity of infection in aged animals involved increased inflammasome activation and loss of γδ T cells that was corrected by ketogenic diet.

Published:

September 12, 2020

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Title:

Effects of Total Red Meat Intake on Glycemic Control and Inflammatory Biomarkers: A Meta-Analysis of Randomized Controlled Trials

Authors:

O'Connor, Lauren E; Kim, Jung Eun; Clark, Caroline M; Zhu, Wenbin; Campbell, Wayne W

Abstract:

ABSTRACT Our objective was to conduct a systematic review and meta-analysis to assess the effects of total red meat (TRM) intake on glycemic control and inflammatory biomarkers using randomized controlled trials of individuals free from cardiometabolic disease. We hypothesized that higher TRM intake would negatively influence glycemic control and inflammation based on positive correlations between TRM and diabetes. We found 24 eligible articles (median duration, 8 weeks) from 1172 articles searched in PubMed, Cochrane, and CINAHL up to August 2019 that included 1) diet periods differing in TRM; 2) participants aged ≥19 years; 3) included either men or women who were not pregnant/lactating; 4) no diagnosed cardiometabolic disease; and 5) data on fasting glucose, insulin, HOMA-IR, glycated hemoglobin (HbA1c), C-reactive protein (CRP), or cytokines. We used 1) a repeated-measures ANOVA to assess pre to post diet period changes; 2) random-effects meta-analyses to compare pre to post changes between diet periods with ≥ vs. <0.5 servings (35g)/day of TRM; and 3) meta-regressions for dose-response relationships. We grouped diet periods to explore heterogeneity sources, including risk of bias, using the National Heart, Lung, and Blood Institute's Quality Assessment of Controlled Interventions Studies. Glucose, insulin, and HOMA-IR values decreased, while HbA1c and CRP values did not change during TRM or alternative diet periods. There was no difference in change values between diet periods with ≥ vs. <0.5 servings/day of TRM [weighted mean differences (95% CIs): glucose, 0.040 mmol/L (−0.049, 0.129); insulin, −0.710 pmol/L (−6.582, 5.162); HOMA-IR, 0.110 (−0.072, 0.293); CRP, 2.424 nmol/L (−1.460, 6.309)] and no dose response relationships (P > 0.2). Risk of bias (85% of studies were fair to good) did not influence results. Total red meat consumption, for up to 16 weeks, does not affect changes in biomarkers of glycemic control or inflammation for adults free of, but at risk for, cardiometabolic disease. This trial was registered at PROSPERO as 2018 CRD42018096031.

Published:

September 10, 2020

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Title:

Traditional nutrition of Indigenous Peoples in the Arctic zone of Western Siberia : Challenges and impact on food security and health

Authors:

Bogdanova, Elena; Lobanov, Andrey; Andronov, Sergei; Popov, Andrei; Kochkin, Ruslan; Morell, Ildikó Asztalos; Lobanov, Andrey; Andronov, Sergei; Popov, Andrei; Kochkin, Ruslan; Morell, Ildikó Asztalos

Abstract:

The chapter presents traditional nutrition as a part of the traditional culture of the nomadic Indigenous population in the Arctic zone of Western Siberia.

Published:

September 10, 2020

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Title:

Gut microbiota in human metabolic health and disease

Authors:

Fan, Yong; Pedersen, Oluf

Abstract:

Published:

September 4, 2020

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Title:

Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling

Authors:

Warren, Eleanor C.; Dooves, Stephanie; Lugarà, Eleonora; Damstra-Oddy, Joseph; Schaf, Judith; Heine, Vivi M.; Walker, Mathew C.; Williams, Robin S. B.

Abstract:

Low-glucose and -insulin conditions, associated with ketogenic diets, can reduce the activity of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, potentially leading to a range of positive medical and health-related effects. Here, we determined whether mTORC1 signaling is also a target for decanoic acid, a key component of the medium-chain triglyceride (MCT) ketogenic diet. Using a tractable model system, Dictyostelium, we show that decanoic acid can decrease mTORC1 activity, under conditions of constant glucose and in the absence of insulin, measured by phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). We determine that this effect of decanoic acid is dependent on a ubiquitin regulatory X domain-containing protein, mediating inhibition of a conserved Dictyostelium AAA ATPase, p97, a homolog of the human transitional endoplasmic reticulum ATPase (VCP/p97) protein. We then demonstrate that decanoic acid decreases mTORC1 activity in the absence of insulin and under high-glucose conditions in ex vivo rat hippocampus and in tuberous sclerosis complex (TSC) patient-derived astrocytes. Our data therefore indicate that dietary decanoic acid may provide a new therapeutic approach to down-regulate mTORC1 signaling.

Published:

September 2, 2020

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Title:

Friend or foe? Large canid remains from Pavlovian sites and their archaeozoological context

Authors:

Wilczyński, Jarosław; Haynes, Gary; Sobczyk, Łukasz; Svoboda, Jiří; Roblíčková, Martina; Wojtal, Piotr

Abstract:

In this paper we discuss recent claims that dogs were first domesticated from wild wolves in the Middle Upper Paleolithic (MUP), about 27 ka BP. According to our data, we think the presence of large canids at the Pavlovian/MUP sites is a result of hunting specialization and not a sign of an early process of dog domestication. Our interpretation is supported by the following observations, whose implications we discuss: (1) Pavlovian faunal assemblages from seven sites in Moravia contain relatively high numbers of large canids; (2) gnaw-marking by large canids occurs with low frequency on the animal bones in these assemblages; (3) the bones of Pavlovian large canids in the sites often have cut marks from skinning, dismembering, and filleting. Whatever the reasons MUP people had for killing wolves, such as for food or for the skins, the effect would have reduced competition for prey between humans and wolves. The relatively high frequency of wolves at Pavlovian sites may have been a side effect of settlement aggregation and long-term occupations of sites, which could have attracted wolves to the settlements, and thus increased the need for humans to reduce their numbers.

Published:

September 1, 2020

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Title:

How isotopic signatures relate to meat consumption in wild chimpanzees: A critical reference study from Taï National Park, Côte d’Ivoire

Authors:

Oelze, Vicky M.; Wittig, Roman M.; Lemoine, Sylvain; Kühl, Hjalmar S.; Boesch, Christophe

Abstract:

The roots of human hunting and meat eating lie deep in our evolutionary past shared with chimpanzees (Pan troglodytes). From the few habituated wild populations, we know that there is considerable variation in the extent to which chimpanzees consume meat. Expanding our knowledge of meat eating frequencies to more, yet unhabituated, populations requires noninvasive, indirect quantitative techniques. We here evaluate the use of stable isotopes to reconstruct meat-eating behavior in wild chimpanzees. We present hair isotope data (n = 260) of two western chimpanzee (P. troglodytes verus) groups from Taï forest (Côte d’Ivoire) and relate them to directly observed amounts of meat consumed, sex/female reproductive state, and group, while controlling for differences between individuals, seasons, and observation efforts. Succeeding seven months of hunting observations, we collected hair of 25 individuals for sequential analysis of δ15N and δ13C. Hunting success in the 7-month study period varied between the groups, with 25 successful hunts in the East group and only 8 in the North group. However, our models only found a direct relationship between amounts of meat consumed and variation within individual hair δ15N values in the East group, but not in the North group and not when comparing between individuals or groups. Although on average East group individuals consumed more than double the amount of meat than North group individuals, their δ15N values were significantly lower, suggesting that differences in microhabitat are substantial between group territories. The effect of sex/female reproductive state was significant in δ15N and δ13C, suggesting it related to access to food or feeding preferences. We conclude that several factors additional to diet are influencing and thus obscuring the isotope ratios in wild chimpanzee hair, particularly when comparing between sexes and social groups.

Published:

September 1, 2020

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Title:

Rethinking the emergence of bone grease procurement

Authors:

Morin, Eugène

Abstract:

The extraction of grease from deliberately comminuted cancellous bone is a low-return activity that has important evolutionary ramifications because it potentially constitutes an early form of resource intensification. From an archaeological standpoint, bone grease extraction is also of significance because it can substantially modify anatomical profiles. Whether this practice is a relatively recent phenomenon or has deep roots reaching back into the Paleolithic, however, remains controversial. The goal of this paper is to cast broader light on the emergence of bone grease procurement by briefly revisiting three French Middle Paleolithic sites (Roc de Marsal, les Pradelles and Grotte du Noisetier) that have been interpreted as potentially early evidence for human processing of cancellous bone for food. To determine whether the published patterns are consistent with this practice, faunal trends at these sites are compared here with recently acquired experimental and ethnographic data on bone comminution activities. The results presented in this paper emphasize the importance of considering human consumption of bone meal as a viable alternative when evaluating competing hypotheses to account for the frequent lack of articular ends in European Paleolithic sites, including many assemblages that show little evidence of carnivore intervention and density-mediated attrition. The analysis also highlights the significance of other activities such as soup making, the use of bone as fuel, ritual disposal of fragments, site cleaning and feeding dogs with pounded bones, which are possible sources of variation when interpreting highly fragmented faunal assemblages. These observations are integrated into a general model focused on the interpretation of bone processing in the archaeological record.

Published:

September 1, 2020

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Title:

The Mid-Holocene bifacial projectile points from Dakhleh Oasis, Egypt: Implications concerning origins of the knapping tradition, changing hunting patterns, the local neolithic, and African cultural independence

Authors:

McDonald, Mary M. A.

Abstract:

The bifacial lithic technology used to produce the numerous arrowheads found in North Africa in the Mid-Holocene is generally thought to have arrived from the Levant, imported with the Neolithic farming tradition after 6200 BCE. However, evidence from Dakhleh Oasis, Egypt, suggests that few Neolithic traits were adopted, while the local bifacial knapping tradition developed independently of the Levant. A group of points from the Dakhleh Bashendi A unit, thought derived from the small points of the Levantine Pottery Neolithic, actually appear much earlier in Dakhleh and evolved locally. Likewise, large points in Dakhleh, usually equated with the large arrowheads of the Levantine PPNB, again developed locally. They were produced by a different chaîne opératoire, while their dimensions and morphology suggest they tipped spears rather than arrows, for use against large Mid-Holocene game animals. A similar range of large points is found in the Fayum Oasis and at Merimde in the Nile Delta, and smaller versions occur westward in the Central Sahara, but in both cases long after they first appeared in Dakhleh. In the Fayum and Merimde, the Dakhleh hollow-based large point was modified to deal with dangerous animals such as crocodiles.

Published:

September 1, 2020

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Title:

The flavors archaeobotany forgot

Authors:

Hastorf, Christine A.; Bruno, Maria C.

Abstract:

Published:

September 1, 2020

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Title:

The importance of large prey animals during the Pleistocene and the implications of their extinction on the use of dietary ethnographic analogies

Authors:

Ben-Dor, Miki; Barkai, Ran

Abstract:

Estimates of the human trophic level and dietary quality during the Paleolithic are the basis for many hypotheses and interpretations regarding human evolution and behavior. We describe an additional factor that could have significantly influenced human evolution and behavior, the availability of large prey animals. Given the importance of large prey and the mounting evidence of the decline in its abundance throughout the Pleistocene, we question the reliability of past reconstructions of the human trophic level that were heavily based on analogies with the recent ethnographic record. We review the ecological and technological records of the Hadza and the Ju/’hoansi (!Kung), two recent hunter-gatherers' groups that dominate the literature as acceptable ethnographic analogs for Paleolithic Africa. We find that their dietary record reflects, as expected by our model, an adaptation to an ecological reality of increased vegetal biomass and reduced large prey biomass that differ substantially from the ecology of most of the Pleistocene but do share analogical trends with the late Upper Paleolithic when the Late Quaternary Megafauna Extinction took place.

Published:

September 1, 2020

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Title:

Ultra-processed foods and early childhood caries in 0-3-year-olds enrolled at Primary Healthcare Centers in Southern Brazil

Authors:

de Souza, Maurício Santos; Vaz, Juliana Dos Santos; Martins-Silva, Thais; Bomfim, Rafael Aiello; Morales Cascaes, Andreia

Abstract:

OBJECTIVE: To investigate the relationship between ultra-processed food consumption and early childhood caries. DESIGN: Cross-sectional analysis of baseline data from a cluster randomised controlled study. Outcomes included the prevalence of children with non-cavitated and cavitated caries. The main exposure was the total daily consumption of ultra-processed foods (up to three times and four times or more), assessed through a FFQ. Potential confounders were socio-demographic characteristics of the child and caregiver/family, child breast-feeding, oral hygiene and use of dental services. Poisson regression using robust variance adjustment was used to estimate prevalence ratios (PR) and their respective 95 % CI. SETTING: Primary Healthcare Centers in an urban area of Pelotas, Southern Brazil. PARTICIPANTS: Children aged 0-3 years (n 309). RESULTS: Consumption of ultra-processed foods four times or more a day was found in 67·6 % of children; 24·4 and 12·0 % presented non-cavitated and cavitated caries, respectively. After adjustment, children who consumed ultra-processed foods four times or more a day were more likely to present both non-cavitated caries (PR 2·25, 95 % CI 1·19, 4·27, P = 0·013) and cavitated caries (PR 3·48, 95 % CI 1·18, 10·30, P = 0·024) compared with those who have consumed them up to three times a day. CONCLUSIONS: Consumption of ultra-processed foods is associated with early childhood caries. Interventions aiming at reducing ultra-processed food consumption should be implemented to improve children's oral health.

Published:

August 27, 2020

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Title:

Association of Higher Arterial Ketone Body Ratio (acetoacetate/β -hydroxybutyrate) with Relevant Nutritional Marker in Hemodialysis Patients

Authors:

Inaba, Masaaki; Kumeda, Yasuroh; Yamada, Shinsuke; Toi, Norikazu; Hamai, Chie; Noguchi, Koichi; Yasuda, Eikichi; Furumitsu, Yutaka; Emoto, Masanori; Ohno, Yoshiteru

Abstract:

Background: An association of higher levels of b-hydroxybutyrate (b-HB) in serum with greater mortality in hemodialysis (HD) patients has been reported. This study examined the signi cance of arterial ketone body ratio (AcAc/b-HB), a relevant marker of energy state, in HD patients. Methods: The levels of arterial AcAc and b-HB, and AcAc/b-HB ratio were determined in 49 HD patients just before undergoing an HD session. Additionally, their changes during the session were examined to investigate their associations with clinical nutritional markers. Results: Arterial b-HB, but not AcAc, was signi cantly higher at the baseline in 25 patients with diabetes mellitus (DM) as compared to 24 non-DM patients, with a signi cant reduction in arterial AcAc/b-HB ratio seen in those with DM. Although the arterial AcAc/b-HB ratio before the HD session was signi cantly higher in the non-DM group, it did not differ signi cantly after the session between the groups, indicating a faster rate of bHB disappearance from circulation in non-DM HD patients during the interdialytic period. Multiple regression analysis, which included age, gender, presence/absence of DM, log HD duration, log b-HB, and log AcAc/b-HB ratio as independent variables, revealed an independent and signi cant association of log AcAc/ b-HB ratio, but not log b-HB, with serum albumin and uric acid. Conclusion: We found that a decreased AcAc/b-HB ratio resulting from increased b-HB, but not increased b-HB itself, was signi cant factor independently associated with decreased serum albumin and uric acid, which are both known as risks for higher mortality in HD patients. Furthermore, it is possible that higher mortality in DM HD patients might be explained by their lower arterial AcAc/b-HB ratio.

Published:

August 24, 2020

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Title:

Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review

Authors:

Astrup, Arne; Magkos, Faidon; Bier, Dennis M.; Brenna, J. Thomas; Otto, Marcia C. de Oliveira; Hill, James O.; King, Janet C.; Mente, Andrew; Ordovas, Jose M.; Volek, Jeff S.; Yusuf, Salim; Krauss, Ronald M.

Abstract:

Central Illustration Figure1Download figure Open in new tab Download powerpoint Highlights • The U.S. Dietary Guidelines recommend the restriction of SFA intake to

Published:

August 18, 2020

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Title:

Effects of Dietary Glycemic Index and Glycemic Load on Cardiometabolic and Reproductive Profiles in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Authors:

Kazemi, Maryam; Hadi, Amir; Pierson, Roger A; Lujan, Marla E; Zello, Gordon A; Chilibeck, Philip D

Abstract:

ABSTRACT Women with polycystic ovary syndrome (PCOS) exhibit cardiometabolic (e.g., insulin resistance) and associated reproductive disruptions. Lifestyle modification (e.g., diet) is recommended as the first-line therapy to manage PCOS; however, a favorable dietary regimen remains unclear beyond energy restriction. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to summarize evidence on impacts of dietary glycemic index (GI) or glycemic load (GL) on cardiometabolic and reproductive profiles to update the International Evidence-based Guideline for the Assessment and Management of PCOS. Databases of MEDLINE, Cochrane, Web of Science, and Scopus were searched through 30 October 2019, and confirmed on 25 March 2020, to identify RCTs (≥8 wk) comparing the effects of diets with lower (LGI/LGL) and higher (HGI/HGL) GI/GL on glucoregulatory outcomes, lipid profile, anthropometrics, and androgen status in PCOS. The primary outcome was HOMA-IR. Data were pooled by random-effects models and expressed as weighted mean differences and 95% CIs. The risk of bias was assessed by the Cochrane tool. Ten RCTs (n = 403) were eligible. Eight evaluated LGI and 2 LGL diets. LGI diets decreased HOMA-IR (−0.78; −1.20, −0.37; I2 = 86.6%), fasting insulin (−2.39; −4.78, 0.00 μIU/mL; I2 = 76.8%), total cholesterol (−11.13; −18.23, −4.04 mg/dL; I2 = 0.0%), LDL cholesterol (−6.27; −12.01, −0.53 mg/dL; I2 = 0.0%), triglycerides (−14.85; −28.75, −0.95 mg/dL; I2 = 31.0%), waist circumference (−2.81; −4.40, −1.23 cm; I2 = 53.9%), and total testosterone (−0.21; −0.32, −0.09 nmol/L; I2 = 8.6%) compared with HGI diets (all: P ≤ 0.05) without affecting fasting glucose, HDL cholesterol, weight, or free androgen index (all: P ≥ 0.07). Some results were contradictory and only described narratively for 2 RCTs that evaluated LGL diets, since inclusion in meta-analyses was not possible. LGI diets improved glucoregulatory outcomes (HOMA-IR, insulin), lipid profiles, abdominal adiposity, and androgen status, conceivably supporting their inclusion for dietary management of PCOS. Further RCTs should confirm these observations and address whether LGI diets improve more patient-pressing complications, including ovulatory cyclicity, infertility, and cardiovascular disease risk in this high-risk population. This review was registered at www.crd.york.ac.uk/PROSPERO as CRD42020175300.

Published:

August 17, 2020

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Title:

Effects of weight loss during a very low carbohydrate diet on specific adipose tissue depots and insulin sensitivity in older adults with obesity: a randomized clinical trial

Authors:

Goss, Amy M.; Gower, Barbara; Soleymani, Taraneh; Stewart, Mariah; Pendergrass, May; Lockhart, Mark; Krantz, Olivia; Dowla, Shima; Bush, Nikki; Garr Barry, Valene; Fontaine, Kevin R.

Abstract:

Insulin resistance and accumulation of visceral adipose tissue (VAT) and intermuscular adipose tissue (IMAT) place aging adults with obesity at high risk of cardio-metabolic disease. A very low carbohydrate diet (VLCD) may be a means of promoting fat loss from the visceral cavity and skeletal muscle, without compromising lean mass, and improve insulin sensitivity in aging adults with obesity.

Published:

August 12, 2020

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Title:

Quantitative Fluxomics of Circulating Metabolites

Authors:

Hui, Sheng; Cowan, Alexis J.; Zeng, Xianfeng; Yang, Lifeng; TeSlaa, Tara; Li, Xiaoxuan; Bartman, Caroline; Zhang, Zhaoyue; Jang, Cholsoon; Wang, Lin; Lu, Wenyun; Rojas, Jennifer; Baur, Joseph; Rabinowitz, Joshua D.

Abstract:

Mammalian organs are nourished by nutrients carried by the blood circulation. These nutrients originate from diet and internal stores, and can undergo various interconversions before their eventual use as tissue fuel. Here we develop isotope tracing, mass spectrometry, and mathematical analysis methods to determine the direct sources of circulating nutrients, their interconversion rates, and eventual tissue-specific contributions to TCA cycle metabolism. Experiments with fifteen nutrient tracers enabled extensive accounting for both circulatory metabolic cycles and tissue TCA inputs, across fed and fasted mice on either high-carbohydrate or ketogenic diet. We find that a majority of circulating carbon flux is carried by two major cycles: glucose-lactate and triglyceride-glycerol-fatty acid. Futile cycling through these pathways is prominent when dietary content of the associated nutrients is low, rendering internal metabolic activity robust to food choice. The presented in vivo flux quantification methods are broadly applicable to different physiological and disease states.

Published:

August 12, 2020

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