Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet

Gao, Xiang; Liu, Xiaofang; Xu, Jie; Xue, Changhu; Xue, Yong; Wang, Yuming

doi:10.1016/j.jbiosc.2014.03.001

Cited by 291 publications

(251 citation statements)

References 42 publications

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“…The recessive disorder cholesterol, lipoprotein, or glucose levels, or hepatic TG or cholesterol levels in apoE null (ApoEKO) mice ( 2, 3 ). On the other hand, in a study using male C57BL/6J mice, TMAO supplementation was associated with signifi cantly decreased plasma TG and TC levels, the opposite of our fi ndings, and increased insulin levels ( 31 ). Moreover, overexpression of FMO3 in Hep3B cells by adenovirusmediated gene transduction led to signifi cantly increased glucose production and lipogenesis, suggesting a direct role for FMO3 in modulating lipid and glucose homeostasis.…”

Section: Discussioncontrasting

confidence: 84%

Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis

Shih

Wang

Lee

et al. 2015

Journal of Lipid Research

278

230

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Section: Discussioncontrasting

confidence: 84%

Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis

Shih

Wang

Lee

et al. 2015

Journal of Lipid Research

278

230

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“…The association of the microbiota with diseases such as cancer (31), diabetes (32), and cardiovascular diseases (33) has been demonstrated. TMAO is a metabolite created in the host liver from microbiota-produced TMA, and it has been associated with several diseases (3)(4)(5)(6)(7)(8)(9)(10). TMA production in the intestine can be suppressed by antibiotics (34,35), but this effect is not complete, and long-term antibiotic treatment may lead to an imbalance in the microbiota (36).…”

Section: Discussionmentioning

confidence: 99%

“…Lowering TMA and TMAO levels in humans could therefore have potentially preventive and therapeutic effects on trimethylaminuria and cardiovascular diseases. TMAO also increased glucose tolerance and adipose tissue inflammation in mice fed a high-fat diet (10), suggesting involvement in the development of diabetes. Structural biology studies of microbiota enzymes are important to guide the discovery of novel inhibitor compounds.…”

Section: Trimethylamine (Tma)mentioning

confidence: 93%

Structure and Function of CutC Choline Lyase from Human Microbiota Bacterium Klebsiella pneumoniae

Kalnins

Kuka

Grı̄nberga

et al. 2015

Journal of Biological Chemistry

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Background:The bacterial glycyl radical enzyme CutC converts choline to trimethylamine, a metabolite involved in pathogenesis of several diseases. Results: The structures of substrate-bound and substrate-free CutC revealed significant differences. Conclusion: Choline binding to the active site triggers a conformational change from the open to closed form. Significance: A novel substrate-driven conformational mechanism and a potential target for drug design have been identified.

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“…Furthermore, results from recent studies in mice fed a high-fat diet also suggest that dietary TMAO may exacerbate impaired glucose tolerance, obstruct hepatic insulin signaling, and promote adipose tissue inflammation (59). The scope of biological processes affected by both TMAO and the TMAO production pathway is just starting to be appreciated, with multiple newly recognized links to chronic cardiometabolic disorders.…”

Section: R E V I E W S E R I E S : G U T M I C R O B I O M Ementioning

confidence: 99%

The contributory role of gut microbiota in cardiovascular disease

2014

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R e v i e w s e R i e s : g u t m i c R o b i o m eSeries Editor: Martin J. Blaser IntroductionCardiovascular disease (CVD) remains the leading cause of death in both the United States and industrialized societies, with growing incidence in developing countries (1). Factors contributing to CVD arise from genetic sources, environmental sources, or a combination of genetic and environmental sources (2). Despite extensive investigations in search of causal genetic variants, such as large-scale GWAS, less than one-fifth of attributable cardiovascular risk has been accounted for from genetic determinants (3, 4). At the same time, major advances in the treatment of atherosclerosis beyond high-potency lipid-lowering agents has not yet materialized (5). Indeed, even with high-potency statin therapy, at least a 50% residual risk remains (6), with the majority of events unchecked. Therefore, there is still ample room for improving our understanding of the processes contributing to CVD pathogenesis, and for improved prevention and treatment of CVD. While the recognizable contribution of genetics to CVD will no doubt significantly increase with time, a reassessment of environmental contributions to CVD pathogenesis and risks for adverse events is certainly worthwhile.Our largest environmental exposure is what we eat. Technically speaking, food is a foreign object that we take into our bodies in kilogram quantities every day. From the latest National Health and Nutrition Examination Survey (NHANES, 2009(NHANES, -2010, the majority of individuals sampled achieved an intermediate or poor Healthy Eating Index (1). However, dietary composition is often difficult to assess, and even precise quantification of dietary intake may not necessarily reveal the many known and unknown factors that may influence the contributions of specific dietary nutrients to disease susceptibility (7). There has also been an overwhelming lack of appreciation at the bedside regarding the intricate and complicated processes that transform ingested food into the myriad metabolites that enter the circulation and fulfill or adversely affect various functional and metabolic processes in the body.Over the past decade we have increasingly begun to appreciate the ecological diversity of microbes living symbiotically within us, a large proportion of which reside within our intestines. We now know that the human gut harbors more than 100 trillion microbial cells, far outnumbering the human host cells of the body (8). Indeed, a sobering fact is that Homo sapiens DNA is estimated to represent less than 10% of the total DNA within our bodies, due to the staggeringly large numbers of microbes that reside in and on us, primarily within our gut (9). Our microbial symbiont guests have coevolved with us and affect a wide range of physiologic and metabolic processes of the body. The major taxa present in gut microbiota consist primarily of 2 major bacterial phyla, Firmicutes and Bacteroidetes, whose proportions appear to remain remarkably stable over time within individu...

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Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet

Cited by 291 publications

References 42 publications

Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis

Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis

Structure and Function of CutC Choline Lyase from Human Microbiota Bacterium Klebsiella pneumoniae

The contributory role of gut microbiota in cardiovascular disease

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