Brian J. Bennett

High dietary B 12 is associated with reduced gut microbial B 12 biosynthesis capacity and lower fecal short-chain fatty acids in healthy United States adults

Margaret A. Hilliard, Andrew S. Oliver, Stephanie M. G. Wilson, Setareh Shahab-Ferdows et autres

Vitamin B12 is acquired through the consumption of animal-source foods and supplements. In animal models, interventions with B12 and/or methionine influence fecal short-chain fatty acid (SCFA) concentration. Yet the relevance of dietary B12 to microbially produced SCFAs in humans is unknown. This …

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Primary-Level Meta-Analysis of Diversity Outbred Mice Identifies a Fasting Plasma Trimethylamine N-Oxide (TMAO) Locus Modified by Sex and Diet

Kristen J. Sutton, Levi W. Evans, Erik R. Gertz, Dawson Budke et autres

Abstract Trimethylamine n-oxide (TMAO) is a plasma metabolite linked to adverse cardiometabolic health with complex regulation involving diet, sex, and host genetics. We explored the role of these factors in the genetic regulation of TMAO by performing a primary-level meta-analysis in 1,482 …

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GSK3α functions as a stemness checkpoint across multiple stem cell states

Duo Wang, Xiukun Wang, Safia Malki, Yanpui Chan et autres

Pluripotent stem cells (PSCs) generate derivatives of all three germ layers; however, robust contribution to chimeric embryos is largely restricted to early pluripotent states. Mouse embryonic stem cells (mESCs), derived from the inner cell mass, readily contribute to chimeras, whereas post-implantation mouse …

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Home-Based Exercise Improves Muscle Oxidative Capacity in Kidney Disease

Gwénaëlle Begue, Armin Ahmadi, Christopher Hayden, Alec Foster et autres

Introduction Muscle impairment in chronic kidney disease (CKD) contributes to decreased physical performance, frailty, and increased mortality. This proof-of-concept randomized controlled study evaluated the efficacy of a 12-week home-based, video-supervised exercise program on muscle endurance in moderate-to-severe nondialysis CKD. Methods Thirty-two sedentary …

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Urinary signatures are associated with calorie restriction-mediated weight loss in obese Diversity Outbred mice

Evan M. Paules, Isis Trujillo‐Gonzalez, Melissa VerHague, Jody Albright et autres

Metabolomic profiles are increasingly being used to identify responders to dietary interventions. Advances using this approach are particularly needed to personalize and enhance the effectiveness of dietary weight loss interventions. Using obese Diversity Outbred (DO) mice that model genetic and phenotypic heterogeneity …

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Exercise Alters the Single-Cell Transcriptome of Peripheral Blood Mononuclear Cells in Persons with CKD

Jennifer Norman, Gwénaëlle Begue, Armin Ahmadi, Jesse Gipe et autres

Background: Persons with chronic kidney disease (CKD) are at increased risk of sarcopenia and frailty, which may be mitigated by increased physical activity. In the ESTEEM-VIDA pilot randomized controlled trial (NCT02923063), we recently demonstrated that a 12-week home-based exercise intervention leads to …

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Trimethylamine- N -Oxide Affects Cell Type–Specific Pathways and Networks in Mouse Aorta to Promote Atherosclerotic Plaque Vulnerability

Jenny Yeuk‐Ki Cheng, Michael L. Cheng, Satyesh K. Sinha, Ingrid Cely et autres

BACKGROUND: -oxide (TMAO) has been significantly linked to atherosclerosis via several mechanisms, but its direct effect on the atherosclerosis-prone vasculature remains unclear. The objective of this study was to characterize the cell type-dependent and independent effects of TMAO on key vascular cell …

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Urinary Signatures Predict Calorie Restriction-Mediated Weight Loss in Obese Diversity Outbred Mice

Evan M. Paules, Isis Trujillo‐Gonzalez, Melissa VerHague, Jody Albright et autres

Predictive analytics encompassing metabolomic profiles are increasingly being used to forecast responders to dietary interventions. Advances using this approach are particularly needed to personalize and enhance the effectiveness of dietary weight loss interventions. Using obese Diversity Outbred (DO) mice that model genetic …

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Hypertension and the Gut Microbiome: A Science Advisory From the American Heart Association

Tao Yang, Katherine Anne Maki, Francine Z. Marques, Jun Cai et autres

Although substantial advancements have been made in hypertension research, translation of this research into new pharmacotherapies remains challenging. The need for new therapies is imperative: 15% to 20% of patients with hypertension have treatment-resistant hypertension, which often persists despite aggressive clinical treatments …

The impact of early-life exposures on growth and adult gut microbiome composition is dependent on genetic strain and parent- of- origin

M. Nazmul Huda, Emer M. Kelly, Keri A. Barron, Jing Xue et autres

BACKGROUND: Early-life exposure to environmental factors can have long-lasting impacts on offspring health into adulthood and therefore is an emerging public health concern. In particular, the impact of maternal environmental exposures such as diet and antibiotic use on the establishment of the …

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A Novel Heterobifunctional ALOX15 Degrader for Treatment of Nasal Polyps

Jonathan E. Phillips, Dyt Fong, Brian J. Bennett, Yue Hao et autres

Abstract ALOX15 encodes a 15-lipoxygenase enzyme that converts multiple fatty acid substrates into a large array of bioactive lipid mediators. A Genome Wide Association Study (GWAS) reported a loss of function missense variant in ALOX15 (rs34210653, Thr560Met, minor allele frequency = 3%) …

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Genetic Risk, Diet, and Lifestyle: Differential Contributions to DXA Body Composition Phenotypes in a Nutritional Cohort

C. Edward Arrington, Debra K. Tacad, Nancy L. Keim, Brian J. Bennett