Short-term high-fat diet increases postprandial trimethylamine- N -oxide in humans

Boutagy, Nabil E.; Neilson, Andrew P.; Osterberg, Kristin L.; Smithson, Andrew T.; Englund, Tessa R.; Davy, Brenda M.; Hulver, Matthew W.; Davy, Kevin P.

doi:10.1016/j.nutres.2015.07.002

Cited by 86 publications

(74 citation statements)

References 15 publications

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“…In the present study, we found that mice fed a WD for 8 weeks developed obesity and dyslipidemia but did not significantly increase plasma glucose levels, confirming the results of a previous study (Carbone et al, 2015). Moreover, an 8 week WD feeding significantly increased plasma TMAO levels in mice, which is consistent with the finding of recent studies in human (Boutagy et al, 2015a,b), suggesting that consumption of WD may alter gut microbiota composition and function, and contribute to elevated circulating TMAO levels.…”

Section: Discussionsupporting

confidence: 91%

“…TMA containing nutrients including L-carnitine and choline are primarily present in WD. Excessive consumption of WD may influence the capacity of the gut microbiota to generate TMA and, consequently TMAO from these nutrients (Boutagy et al, 2015b). Additionally, consumption of WD can rapidly alter the composition of gut microbiota (David et al, 2014), leading to increased production of TMAO (Kitai et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Altered microbiota composition may influence gut microbial TMA production and TMAO synthesis (Chen et al, 2016). Indeed, recent studies have demonstrated that consumption of WD lead to increases in circulating TMAO levels in human (Boutagy et al, 2015a,b). To date, however, no studies have tested whether TMAO plays a role in the pathogenesis of cardiac dysfunction in obesity.…”

Section: Introductionmentioning

confidence: 99%

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Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide Contributes to Cardiac Dysfunction in Western Diet-Induced Obese Mice

Chen

Zheng²,

Feng³

et al. 2017

Front. Physiol.

227

160

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Excessive consumption of diets high in sugars and saturated fat, frequently known as western diet (WD), may lead to obesity and metabolic syndrome. Recent evidence shows that WD-induced obesity impairs cardiac function, but the underlying mechanisms are not fully understood. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of specific dietary nutrients, has emerged as a key contributor to cardiovascular disease pathogenesis. We tested the hypothesis that elevated circulating TMAO levels contribute to cardiac dysfunction in WD-induced obesity. CD1 mice were fed a normal diet (ND) or a WD, without or with 1.0% 3,3-Dimethyl-1-butanol (DMB, an inhibitor of trimethylamine formation) in drinking water for 8 weeks. Compared with mice fed a ND, mice fed a WD showed a significant increase in body weight and dyslipidemia, and had markedly higher plasma TMAO levels at the end of the feeding protocol. Echocardiography revealed that cardiac systolic and diastolic function was impaired in mice fed a WD. DMB treatment had no effects on body weight and dyslipidemia, but significantly reduced plasma TMAO levels and prevented cardiac dysfunction in mice fed a WD. In addition, mice fed a WD had elevated expression of pro-inflammatory cytokines tumor necrosis factor-α and interleukin IL-1β, decreased expression of anti-inflammatory cytokine IL-10, and increased interstitial fibrosis in the hearts, all of which were prevented by DMB treatment. Notably, DMB treatment also reduced plasma TMAO levels in mice fed a ND but did not alter other parameters. These results suggest that consumption of a WD increases circulating TMAO levels, which lead to cardiac inflammation and fibrosis, contributing to cardiac dysfunction. Interventions that reduce circulating TMAO levels may be a novel therapeutic strategy for prevention and treatment of WD-induced cardiac dysfunction.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide Contributes to Cardiac Dysfunction in Western Diet-Induced Obese Mice

Chen

Zheng²,

Feng³

et al. 2017

Front. Physiol.

227

160

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“…It has been reported that a high-fat diet led to alterations in gut microbial composition16–18 that have been associated with insulin resistance 18 41. In an experimental study of non-obese adults, a high-fat diet increased postprandial plasma TMAO levels (after 4 hours of the high-fat meal challenge) whereas postprandial plasma choline or L-carnitine levels did not change after eating the high-fat diet 20. On the other hand, the study did not find a significant increase in fasting plasma TMAO concentrations following the short-term (5-day) high-fat diet intervention in the non-obese men 20.…”

Section: Discussionmentioning

confidence: 96%

“…In an experimental study of non-obese adults, a high-fat diet increased postprandial plasma TMAO levels (after 4 hours of the high-fat meal challenge) whereas postprandial plasma choline or L-carnitine levels did not change after eating the high-fat diet 20. On the other hand, the study did not find a significant increase in fasting plasma TMAO concentrations following the short-term (5-day) high-fat diet intervention in the non-obese men 20. Another study of normal-weight individuals showed that a 4 week high-fat diet significantly increased plasma TMAO concentrations, whereas plasma L-carnitine or choline concentrations did not increase in the high-fat diet group 21.…”

Section: Discussionmentioning

confidence: 96%

Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial

Heianza

Sun

et al. 2018

Gut

141

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ObjectiveAlterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and its nutrient precursors (choline and L-carnitine) were associated with improvements in glucose metabolism and diabetes-related amino acids in a weight-loss diet intervention.DesignWe included 504 overweight and obese adults who were randomly assigned to one of four energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline and L-carnitine levels after the intervention were calculated.ResultsGreater decreases in choline and L-carnitine were significantly (p<0.05) associated with greater improvements in fasting insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. The reduction of choline was significantly related to 2-year improvements in glucose and insulin resistance. We found significant linkages between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin and HOMA-IR (pinteraction <0.05); a greater increase in TMAO was related to lesser improvements in the outcomes among participants who consumed a high-fat diet. In addition, ΔL-carnitine and Δcholine were significantly related to changes in amino acids (including branched-chain and aromatic amino acids). Interestingly, the associations of ΔTMAO, Δcholine and ΔL-carnitine with diabetes-related traits were independent of the changes in amino acids.ConclusionOur findings underscore the importance of changes in TMAO, choline and L-carnitine in improving insulin sensitivity during a weight-loss intervention for obese patients. Dietary fat intake may modify the associations of TMAO with insulin sensitivity and glucose metabolism.Trial registration numberNCT00072995.

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Effects of Gut Bacteria Depletion and High‐Na⁺ and Low‐K⁺ Intake on Circulating Levels of Biogenic Amines

Blaženović

Li³

et al. 2018

Molecular Nutrition Food Res

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Scope High‐sodium and low‐potassium (HNaLK) content in Western diets increases the risk of hypertension and cardiovascular disease (CVD). It is investigated if the dietary minerals interact with gut bacteria to modulate circulating levels of biogenic amines, which are implicated in various pathologies, including hypertension and CVD. Methods and results Using a metabolomic approach to target biogenic amines, the effects of gut bacteria depletion and HNaLK intake on circulating levels of biogenic amines in rats are examined. Forty‐five metabolites whose plasma levels are significantly altered by gut bacteria depletion (p < 0.05) are found, indicating their regulation by gut bacteria. Many of them are not previously linked to gut bacteria; therefore, these data provide novel insights into physiological or pathological roles of gut bacteria. A number of plasma metabolites that are altered both by gut bacteria and HNaLK intake are also found, suggesting possible interactions of the diet and gut bacteria in the modulation of these metabolites. The diet effects are observed with significant changes in the gut bacterial taxa Porphyromonadaceae and Prevotellaceae (p < 0.05). Conclusion The dietary minerals may regulate abundances of certain gut bacteria to alter circulating levels of biogenic amines, which may be linked to host physiology or pathology.

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Short-term high-fat diet increases postprandial trimethylamine- N -oxide in humans

Cited by 86 publications

References 15 publications

Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide Contributes to Cardiac Dysfunction in Western Diet-Induced Obese Mice

Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide Contributes to Cardiac Dysfunction in Western Diet-Induced Obese Mice

Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial

Effects of Gut Bacteria Depletion and High‐Na⁺ and Low‐K⁺ Intake on Circulating Levels of Biogenic Amines

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Short-term high-fat diet increases postprandial trimethylamine- N -oxide in humans

Cited by 86 publications

References 15 publications

Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide Contributes to Cardiac Dysfunction in Western Diet-Induced Obese Mice

Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide Contributes to Cardiac Dysfunction in Western Diet-Induced Obese Mice

Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial

Effects of Gut Bacteria Depletion and High‐Na+ and Low‐K+ Intake on Circulating Levels of Biogenic Amines

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Product

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Effects of Gut Bacteria Depletion and High‐Na⁺ and Low‐K⁺ Intake on Circulating Levels of Biogenic Amines