Harvard Scientists Reveal New Way to Tackle Diabetes and Obesity

JAKARTA - Research at Harvard University, United States, has found a group of metabolites that move from the gut to the liver, then to the heart to be distributed throughout the body. These compounds play an important role in regulating liver metabolism and affecting insulin sensitivity, thus potentially helping the treatment of obesity and type 2 diabetes. The results of this study were published in the journal Cell Metabolism.

"The hepatic vena porta vein carries most of the blood from the intestine to the liver," explained Vitor Rosetto Muñoz, lead author of the study, quoted from the Science Daily website.

"This means that this is the first pathway that receives products from the gut microbiome. In the liver, these compounds can be changed, combined, or discarded, before finally entering the blood circulation of the whole body," he continued.

By comparing blood that comes directly from the gut and blood circulating throughout the body, researchers can see how metabolites from the gut microbiome affect liver metabolism and overall body health. This research was conducted while Muñoz was an intern at the Joslin Diabetes Center, Harvard Medical School, under the guidance of Carl Ronald Kahn.

Over the past few years, the gut microbiome has been known to play an important role in metabolic disorders. Previous studies have shown that obese and type 2 diabetics have a different composition of gut microbiota than healthy individuals. However, it is still unclear which bacteria or microbial products are most influential.

To answer this, researchers examined metabolites in the blood of mice with different risk of obesity and diabetes. Blood samples were taken from the hepatic vena porta and peripheral blood.

"Usually, research only looks at metabolites in feces or peripheral blood. In fact, it does not fully describe what first reaches the liver, a very important metabolic organ and associated with many diseases," said Muñoz.

In healthy mice, 111 metabolites were found in the hepatic portal vein, while in mice prone to obesity and diabetes, the number dropped drastically to 48 after being fed a high-fat diet. This suggests that environmental factors such as diet strongly influence the distribution of metabolites.

Differences in metabolite profiles were also seen between susceptible and more resistant mice to metabolic syndrome, confirming the role of genetic factors.

"This shows that the environment and the genetics of the body interact in a complex way with the gut microbiome. As a result, the combination of metabolites sent to the liver and then to the bloodstream can be different. These metabolites are likely to play a role in the process of obesity, diabetes, and metabolic syndrome," explained Muñoz.

When the microbiome of mice was altered using antibiotics, the composition of metabolites also changed. One of the metabolites that increased was mesaconate, which is involved in the Krebs cycle, the main pathway for generating cellular energy.

When liver cells are exposed to mesaconate, insulin signaling improves and genes that regulate fat formation and burning become more balanced. This process is important for maintaining metabolic health.

"The metabolites found in these two blood locations play a major role in mediating the influence of the microbiome on liver metabolism and the development of insulin resistance in type 2 diabetes, especially in relation to the consumption of high-fat foods," said Muñoz.

In the future, researchers will examine each metabolite in more depth in order to find new compounds that have the potential to be a therapy for metabolic diseases.