| Author |
Zhang, Y; Wang, XM; Lin, J; Liu, J; Wang, K; Nie, QX; Ye, C; Sun, LL; Ma, YP; Qu, RZ; Mao, YJ; Zhang, XG; Lu, H; Xia, PY; Zhao, DY; Wang, G; Zhang, ZP; Fu, W; Jiang, CT; Pang, YL |
| Abstract |
Time-restricted feeding (TRF) is a potent dietary intervention for improving metabolic diseases, including metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis (MASLD/MASH). However, the mechanism of this efficacy has remained elusive. Here, we show that TRF improves MASLD, which is associated with a significant enrichment of Ruminococcus torques (R. torques). Mechanistically, R. torques suppresses the intestinal HIF-2a-ceramide pathway via the production of 2-hydroxy-4-methylpentanoic acid (HMP). We identify rtMor as a 4-methyl-2-oxopentanoate reductase that synthesizes HMP in R. torques. Finally, we show that either the colonization of R. torques or oral HMP supplementation can ameliorate inflammation and fibrosis in a MASH mouse model. These findings identify R. torques and HMP as potential TRF mimetics for the treatment of metabolic disorders. |
