Microbiome, trimethylamine N-oxide, and cardiometabolic disease

Tang, W.H. Wilson; Hazen, Stanley L.

doi:10.1016/j.trsl.2016.07.007

Cited by 110 publications

(84 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Aortic lesion size was positively correlated with Fmo3 expression levels in Apoe −/− mice (114), and increased levels of TMAO were associated with thrombosis risk and with a 4-fold increased mortality risk (101, 125). As more attention is focused on the impact of TMAO on cardiovascular disease risk, investigators should keep in mind the innate sex difference in TMAO levels and Fmo3 expression (105). Taken together, these studies indicate that complex relationships exist between sex, gut microbiota, and metabolic health, and underscore the importance of further mechanistic studies.…”

Section: The Gut Microbiome and Sex Differences In Metabolic Syndmentioning

confidence: 99%

Genetic Basis for Sex Differences in Obesity and Lipid Metabolism

2017

View full text Add to dashboard Cite

Men and women exhibit significant differences in obesity, cardiovascular disease and diabetes. To provide better diagnosis and treatment for both sexes, it is important to identify factors that underlie the observed sex differences. Traditionally, sex differences have been attributed to the differential effects of male and female gonadal secretions (commonly referred to as “sex hormones”), which do substantially influence many aspects of metabolism and related diseases. Less appreciated as a contributor to sex differences are the fundamental genetic differences between males and females, which are ultimately determined by the presence of an XX or XY sex chromosome complement. Here we review the mechanisms by which gonadal hormones and sex chromosome complement each contribute to lipid metabolism and associated diseases, and the current approaches that are used to study them. We focus particularly on genetic approaches including genome-wide association studies in humans and mice, “–omics” and “systems genetics” approaches, and unique experimental mouse models that allow distinction between gonadal and sex chromosome effects.

show abstract

Section: The Gut Microbiome and Sex Differences In Metabolic Syndmentioning

confidence: 99%

Genetic Basis for Sex Differences in Obesity and Lipid Metabolism

2017

View full text Add to dashboard Cite

show abstract

“…For example, elevated TMAO levels are strongly correlated with increased risk of adverse cardiovascular outcomes, including heart attack, stroke and death risk (Tang and Hazen, 2014, 2017; Tang et al, 2015; Kitai et al, 2016; Li et al, 2017). Elevated TMAO levels also exacerbate pressure overload-induced heart failure (Organ et al, 2016) and prolong hypertensive effect of angiotensin II (Ufnal et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Elevated Circulating Trimethylamine N-Oxide Levels Contribute to Endothelial Dysfunction in Aged Rats through Vascular Inflammation and Oxidative Stress

et al. 2017

View full text Add to dashboard Cite

Vascular endothelial dysfunction, a characteristic of the aging process, is an important risk factor for cardiovascular disease in aging. Although, vascular inflammation and oxidative stress are major contributors to endothelial dysfunction in aging, the underlying mechanisms during the aging process are not fully understood. Accumulating evidence reveals that gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) is implicated in the pathogenesis of many cardiovascular diseases. We tested the hypothesis that aging increases circulating TMAO levels, which induce vascular inflammation and oxidative stress, resulting in age-associated endothelial dysfunction. Old (22-mo-old) and young (4-mo-old) Fischer-344 rats were treated without (control) or with 1.0% 3,3-Dimethyl-1-butanol (DMB, an inhibitor of trimethylamine formation) in drinking water for 8 weeks. Compared with young control group, old control group had markedly higher plasma TMAO levels, which were reduced by DMB treatment. Endothelium-dependent relaxation of aorta in response to acetylcholine was impaired in old control group compared with young control group as indicated by decreased maximal relaxation (Emax) and reduced area under the curve (AUC). Emax and AUC were both normalized in old rats treated with DMB. No difference in endothelial-independent relaxation in response to sodium nitroprusside was observed among groups. Molecular studies revealed that old control group exhibits increased expression of proinflammatory cytokines and superoxide production, and decreased expression of endothelial nitric-oxide synthase (eNOS) in the aorta, all of which were restored by DMB treatment. These results suggest that aging increases circulating TMAO levels, which may impair eNOS-derived NO bioavailability by increasing vascular inflammation and oxidative stress, contributing to aging-associated endothelial dysfunction.

show abstract

“…These processes are strongly associated with numerous conditions ranging from hypertension and diabetes to heart and renal diseases (6).…”

Section: Contextmentioning

confidence: 99%