Not eating after 5pm can improve fatty liver disease. The Peking University team confirmed that intestinal bacteria play a key role in this
2024-07-31
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Typesetting丨Shui ChengwenMetabolic dysfunction-related fatty liver disease（MASLD）It affects approximately one quarter of the population and imposes a significant health and economic burden on society.MASLD includes a variety of different liver manifestations, ranging from liver fattranssexualto more invasiveMetabolic dysfunction-related steatohepatitis（MASH）The latter is characterized by necroinflammation and fibrosis and may progress toCirrhosisevenHepatocellular carcinoma（HCC）Slowing down the progression of MASLD, especially reversing confirmed MASH, is the focus of clinical treatment. Given its complex pathology and the lack of approved medical interventions,Active diet and lifestyle interventionsremains the main option for its management but is limited by poor compliance.Adjusting dietary intake, eating frequency, and eating time windows has become a powerful way to improve and delay the onset of disease and aging.Time-restricted eating（Time-restricted feeding，TRF）, which restricts daily eating to a 4-12 hour period without restricting calorie intake, is considered an effective dietary and lifestyle intervention that can improve and delay the onset of disease. Previous studies have shown that time-restricted eating can reduce weight, improve insulin resistance, and inhibit liver lipid accumulation. However, the specific molecular mechanisms by which this dietary pattern brings benefits remain unclear.July 29, 2024Peking University Third HospitalPang Yanli、Jiang Changtao、Fu Wei、Zhang Zhipengand Beijing Chaoyang Hospital Affiliated to Capital Medical UniversityWang Guanget al. in CellCell Metabolism Published an article titled:A microbial metabolite inhibits the HIF-2α-ceramide pathway to mediate the beneficial effects of time-restricted feeding on MASH research paper.Time-restricted eating（TRF）An effective dietary intervention to improve metabolic diseases, including metabolic dysfunction-associated fatty liver disease/metabolic dysfunction-associated steatohepatitis（MASLD/MASH）However, the mechanism of this therapeutic effect has remained unclear.Gut Microbiome（Gut Microbiota）The composition of the host is a key factor in regulating host metabolism.Gut microbiota is susceptible to dietary characteristics(e.g. the amount and composition of lipids in the diet)。Excessive food intake, food shortages, and even changes in dietary cycles can affect the gut microbiome.Time-restricted eating（TRF）A high-fat diet can be partially resumed（HFD）Periodic fluctuations in the gut microbiota of mice fed a diet increase the diversity of the gut microbiota and affect host metabolism, suggesting thatThe gut microbiota may play an important role in the benefits of time-restricted feeding.Microbial metabolites are considered key mediators of communication between the microbiota and the host, maintaining the physiological functions of the host.Do gut microbiota and microbial metabolites contribute to the effects of time-restricted feeding onMetabolic dysfunction-associated fatty liver disease/Metabolic dysfunction-associated steatohepatitis（MASLD/MASH）The impact remains to be explored.In this latest study, the research team studiedMetabolic fatty liver disease（MASLD）Human patients and mouse models were treated with 10-hourTime-restricted eating（TRF）Program as an intervention to exploreTime-restricted eating（TRF）Potential mechanisms for improvement of MASLD.The research team found, in 19 human patients with MASLD10 hoursTime-restricted eating（TRF）,themAfter four weeks of eating between 7am and 5pm and fasting for the remaining 14 hours, their liver function improved.Further analysis showed that10 hoursTime-restricted eating（TRF）After that, the intestinal microbiotaRuminococcus contortus（Ruminococcus torques）abundance increased, and colonization of this intestinal bacterium was sufficient to simulateTime-restricted eating（TRF）Beneficial effects on MASLD/MASH.Mechanistically, Ruminococcus contortus produces metabolites2-Hydroxy-4-methylvaleric acid（HMP）Inhibits the intestineHIF-2α-Ceramidepassage, thusImprove MASLD/MASH.The study also determinedrtMorIt is the 4-methyl-2-oxopentanoate reductase that synthesizes HMP in Ruminococcus contortus.Finally, the research team further confirmed that both colonization with Ruminococcus contortus and oral HMP supplementation could improve inflammation and fibrosis in the MASH mouse model. These findings identify Ruminococcus contortus and its metabolite HMP as potential time-restricted feeding mimics for the treatment of metabolic disorders.Overall, the study determinedRuminococcus contortus（Ruminococcus torques）and its metabolites2-Hydroxy-4-methylvaleric acid（HMP）existTime-restricted eating（TRF）Middle PairMetabolic dysfunction-associated fatty liver disease/Metabolic dysfunction-associated steatohepatitis（MASLD/MASH）The beneficial effects of Ruminococcus contortus or its metabolite HMP may be developed as probiotics or drug therapies for the treatment of MASLD/MASH.In addition to the dailyTime-restricted eating（TRF）outside,5:2 Intermittent Fasting（5A2F）Another popularDietary intervention, i.e. 5 free-eating days and 2 fasting days out of 7 days per week。research teamRecruited15People with metabolic fatty liver disease（MASLD）of participants took4Weeks of 5A2F dietary intervention, the results showed thatAfter 4 weeks of 5A2F intervention, participants' liver damage markers and triglyceride levels were significantly reduced, while their body mass index（BMI）It also reducesFurther analysis showed thatTheir levels of Ruminococcus contortus and its metabolite HMP were significantly increased, which further confirmedRuminococcus contortus-HMP may also be involved5:2 Intermittent Fasting（5A2F）Mediated improvement process of MASLD. set upStar, don't miss the wonderful tweets
