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written by | song wenfa

fatty liver disease associated with metabolic dysfunction（MASLD）, affecting a quarter of the world's population, is also the most common type of chronic liver disease in china, with more than 150 million patients in my country. currently, no drug has been approved to treat non-alcoholic fatty liver disease, and patients can only intervene through diet and exercise changes. slowing the progression of masld, especially reversing established metabolic-related steatohepatitis（MASH）, is the focus of clinical treatment.

in recent years, fasting has become the new darling of the scientific community. fasting has been shown to reduce weight and extend the lifespan of animals. in fact, a growing number of studies show that fasting has many health benefits, including improving metabolic health, preventing or delaying diseases associated with aging, and even slowing the growth of tumors.

recently,beijing universityof researchers in " Cell Metabolism "the journal published an article entitled"A microbial metabolite inhibits the HIF-2α-ceramide pathway to mediate the beneficial effects of time-restricted feeding on MASH "research paper.

research shows thatfasting for 14 hours a day can improvefatty liverthis improvement was associated with an increase in the abundance of ruminococcus torques in the intestine. further studies have found that colonization of ruminococcus torques or oral supplementation of its metabolite 2-hydroxy-4-methylvaleric acid (hmp) can improve liver inflammation and fibrosis.。

the results suggest that ruminococcus and its metabolite hmp may be able to mimic the benefits of intermittent fasting in improving fatty liver disease, providing a new strategy for people who cannot adhere to intermittent fasting.

in this study, the researchers conducted a clinical intervention study, recruiting 19 patients with masld and implementing a 4-week intermittent fasting program, where participants could eat as much as they wanted from 7 a.m. to 5 p.m. each day.(10 hours after eating), fasting at other times, and collecting stool and plasma samples before and after intermittent fasting, and also testing indicators of liver function and dyslipidemia.

the results showed that after 4 weeks,intermittent fasting improved participants' liver damage markers, which lowered serum alanine aminotransferase（ALT）, aspartate aminotransferase（AST）level.

in addition, intermittent fasting also reduced the participants' liver fatty degeneration index.（HSI）, triglycerides（TG）, body mass index（BMI），it shows that intermittent fasting improves fatty liver。

analysis of fecal samples revealed that intermittent fasting increased the alpha diversity of intestinal flora and significantly increased the abundance of r. torques and c. hathewayi. in the high-fat-induced masld mouse model, results consistent with those in humans were found, and it was found that intestinal flora played an important role in intermittent fasting intervention.

next, the researchers verified which bacterial flora mainly mediated the improvement of masld induced by intermittent fasting in a mouse model. the analysis found thatthe one who improved the fatty liver index was r.torques。

r.torques mediates the improvement of masld induced by light fasting

mechanistic analysis revealed that higher levels of r. torques inhibited intestinal hypoxia-inducible factor 2α by producing hmp（HIF-2α）, thereby inhibiting the hif-2α-ceramide pathway and improving masld. previously, researchers found that intestinal hif-2α can increase the synthesis of ceramide and aggravate the development of masld.

the researchers also found thatcolonization with ruminococcus or oral supplementation with hmp can inhibit intestinal ceramide levels in mouse models and improve liver inflammation and fibrosis, indicating that both r. torques and hmp administration are effective means to prevent and treat fatty liver.

finally, the researchers recruited 15 patients with masld and conducted a 4-week 5:2 fasting intervention. they found that after the 4-week intervention, the participants' liver damage indicators and tg levels decreased significantly. in addition, after the 5:2 fasting intervention, the levels of r.torques and hmp increased significantly, further confirming that r.torques and hmp may be involved in the 5:2 fasting-mediated improvement of masld.

in conclusion, the results suggest that r. torques and its metabolite hmp can improve masld/mash, which depends on the inhibition of the hif-2α-ceramide pathway, and is a new mechanism by which intermittent fasting directly affects hepatic steatosis. since most people find it difficult to adhere to intermittent fasting regimens, this study provides a new method for people to simulate intermittent fasting regimens.