- High levels of trimethylamine oxide (TMAO) are associated with a higher risk of severe cardiovascular events, such as heart attack and stroke.
- TMAO is a chemical produced by gut bacteria during digestion of key nutrients - choline, lecithin and carnitine.
- Mice that had a missing or deactivated flavin-containing monooxygenase 3 (FMO3) gene which converts TMAO into its active form, were protected from obesity.
Gut bacteria which helps in the digestion of food may help prevent obesity and insulin resistance, according to a recent study done by the researchers at the Cleveland clinic.
The team showed that blocking a specific intestinal microbial pathway can prevent obesity and insulin resistance, as well as cause fat tissue to become more metabolically active.
The research team, led by J. Mark Brown, Ph.D., of Cleveland Clinic's Lerner Research Institute, studied the metabolic pathway that creates trimethylamine oxide (TMAO), a chemical produced by gut bacteria during digestion of key nutrients - choline, lecithin and carnitine - found abundantly in animal products, such as red meat, processed meats, egg yolks and liver.
Dr. Brown's colleague on the current study - Stanley Hazen, M.D., Ph.D. - previously showed that high levels of TMAO are associated with a higher risk of severe cardiovascular events, such as heart attack and stroke.
Since cardiovascular disease and obesity are so closely linked, the team hypothesized that TMAO may also be involved in metabolic pathways that lead to obesity. They focused on a host enzyme called flavin-containing monooxygenase 3(FMO3), which converts TMAO into its active form.
They discovered that mice that had a missing or deactivated FMO3 gene were protected from obesity, even when fed a high-fat, high-calorie diet. Furthermore, the FMO3-negative mice showed higher expression of genes associated with beige or brown fat cells, which are more metabolically active than white fat cells.
The study confirmed in 435 patients that high levels of TMAO are associated with higher incidence of Type 2 diabetes.
"Obesity, diabetes and cardiovascular disease are strongly linked. While the microbiome has been shown to affect cardiovascular disease, there is as yet no concrete evidence of precisely how gut bacteria influence obesity," Brown said.
These findings shed light on a possible way to manipulate the microbiome with therapeutics to combat our obesity and diabetes epidemic.
"Given the numerous strong associations of the gut microbe-driven TMAO pathway with human disease, this work has broad implications for drug discovery efforts targeting gut microbes themselves," said Dr. Hazen, chair of the Department of Cellular & Molecular Medicine for the Lerner Research Institute.
"However, additional work is needed to better understand the entire pathway and the links between TMA, FMO3, TMAO and human health."
- Rebecca C. Schugar et al., The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue, Cell Reports (2017) http:dx.doi.org/10.1016/j.celrep.2017.05.077.