Altering gut bacteria pathways may stimulate fat tissue to prevent obesity

Altering gut bacteria pathways may stimulate fat tissue to prevent obesity

Cleveland Clinic researchers have uncovered a biological link between gut bacteria metabolism and obesity. 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 study was recently published in Cell Reports.

The research team 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.

Authors 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.

Antisense oligonucleotide-mediated knockdown or genetic deletion of the TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) conferred protection against obesity in mice. Complimentary mouse and human studies indicate a negative regulatory role for FMO3 in the beiging of white adipose tissue.

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," author said. "These findings shed light on a possible way to manipulate the microbiome with therapeutics to combat our obesity and diabetes epidemic."