Gut Microbiota Metabolite TMA May Mediate the Effects of TMAO on Glucose and Lipid Metabolism in C57BL/6J Mice

Abstract

ScopeGut microbiota can convert a variety of alkaloids and TMAO into TMA, which is then transported by the blood to the liver, and converted into TMAO. In recent years, TMAO has attracted wide attention as a metabolic risk factor in cardiovascular disease, diabetes, and other diseases. However, it is still unclear about the role of gut microbial metabolite TMA in the adverse health impacts of TMAO.Methods and resultsMale C57BL/6J is treated with intraperitoneal (i.p.) or oral TMAO for 8 weeks, the area under the OGTT curve of oral group is significantly increased by about 15% compared to the control and injection groups. Serum triglyceride levels in the oral group are significantly higher by 28.2% and 24.6% than those in the control and injection groups, respectively. Meanwhile, cholesterol content in serum is significantly elevated by 27.6% and 30.7%. Similarly, proinflammatory factors gene expressions are significantly increased with oral but not i.p. TMAO intervention. Furthermore, transformation in HepG2 cells shows that TMAO could not be converted into TMA by hepatocytes.ConclusionThe adverse effects of TMAO on glucose and lipid metabolism in C57BL/6J mice may act through gut microbiota metabolite TMA.

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“…TMAO has been shown to have a causal relationship with atherosclerosis and kidney function. , While for others, only correlations were observed, which means the enhanced TMAO level may be only a feedback mechanism against disease development or could be used as a biomarker rather than an inducer. Moreover, there are animal studies shown that TMA, not TMAO, is responsible for the adverse effects. ,, For different diseases, it further investigation.…”

“…Moreover, there are animal studies shown that TMA, not TMAO, is responsible for the adverse effects. 100,108,114 For different diseases, it further investigation.…”

“…6 However, a latest study pointed out that TMAO ingested through the digestive tract may cause various adverse metabolic impacts including impaired glucose tolerance via comparative study of the metabolic effects of TMAO ingestion through the digestive tract or not, which means gut microbial conversion of TMAO into TMA plays an important part. 108 Moreover, a 4442 older adults involved prospective cohort study pointed out that plasma TMAO and related metabolites such as carnitine, betaine, and choline et al were not significantly associated with type 2 diabetes among older adults. 109 There was also a positive association between plasma TMAO and gestational diabetes mellitus or diabetic retinopathy.…”

“…Moreover, dietary TMAO significantly enhanced fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) in HFD-fed mice, which exacerbated the impaired glucose tolerance . However, a latest study pointed out that TMAO ingested through the digestive tract may cause various adverse metabolic impacts including impaired glucose tolerance via comparative study of the metabolic effects of TMAO ingestion through the digestive tract or not, which means gut microbial conversion of TMAO into TMA plays an important part . Moreover, a 4442 older adults involved prospective cohort study pointed out that plasma TMAO and related metabolites such as carnitine, betaine, and choline et al were not significantly associated with type 2 diabetes among older adults …”