Bile acid will cure obesity and fatty degeneration of the liver

An international team of researchers has demonstrated that one of the bile acids, namely glycine-beta-muricholic acid (Gly-MCA), prevents and eliminates the manifestations of fatty liver infiltration in mice. Moreover, this compound can help in the treatment of a number of metabolic disorders, including type 2 diabetes and obesity.

As part of the study, mice with obesity and diabetes mellitus, contained in a fat-rich diet, received glycine-beta-muricholic acid in tablet form. The result was a smaller amount of adipose tissue and less pronounced resistance of tissues to insulin compared to animals of the control group.

The authors demonstrated that glycine-beta-muricholic acid inhibits the farnesoid X-receptor (FXR), a transcription factor that regulates the expression of certain genes in intestinal and liver tissues. According to one of the leaders of the study, Frank Gonzalez from the US National Institute of Oncology, in intestinal conditions, depending on the ratio of conjugated and unconjugated bile acids, bacteria can activate or inhibit this receptor by modifying the pool of bile acids.

The farnesoid X-receptor plays a key role in maintaining metabolism by registering and regulating the amount of bile acids, fats and glucose in the body. The involvement of this receptor in the production and metabolism of fats may partly explain the ability of glycine-beta-muricholic acid therapy to reduce the severity of obesity. However, this issue needs further study.

The authors note that a very small dose of the compound was sufficient for mice to obtain positive metabolic changes. An equivalent dose for a person can be taken once a day as part of one tablet. They also add that glycine-beta-muricholic acid therapy gave good results both in diet-induced and genetically determined forms of fatty liver infiltration and obesity.

The farnesoid X-receptor has been identified as a promising target for the treatment of fatty liver infiltration and obesity for quite a long time, however, the search for a compound that effectively affects it in a complex and even somewhat chaotic digestive system turned out to be a difficult task.

Since microorganisms, such as lactic acid or lacto-bacteria, usually break down bile acids inhibiting the farnesoid X-receptor, the researchers had to screen a large number of bile acids in order to search for molecules resistant to the enzymatic activity of bacteria. Glycine-beta-muricholic acid turned out to be resistant to lactobacillus enzymes.

The authors note that ideally they would like to obtain more effective glycine-beta-muricholic acid derivatives that are more resistant to bacterial hydrolases and have a more powerful ability to selectively inhibit the farnesoid X receptor. It may also be advisable to search for alternative compounds that have a similar effect and, possibly, more effective.

In any case, there is still a lot of work ahead devoted to a detailed study of the mechanism of action of glycine-beta-muricholic acid, as well as conducting experiments on other animal models and, ultimately, clinical studies.

It should also be noted that, despite the fact that bile acids are practically not used in medicine in Western countries, the bile of various animals is used in folk medicine in Asian countries and is mentioned in ancient medical practices.

Article by Changtao Jiang et al. The intestinal-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction is published in the journal Nature Communications.

Evgeniya Ryabtseva

Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Pennsylvania State University: Pill that targets gut receptor treats fatty liver disease, obesity in mice.