Intestinal TM6SF2 protects against metabolic dysfunction-associated steatohepatitis through the gut-liver axis.

ABSTRACT: Transmembrane-6 superfamily member 2 (TM6SF2) regulates hepatic fat metabolism and is associated with metabolic dysfunction-associated steatohepatitis (MASH). TM6SF2 genetic variants are associated with steatotic liver disease. The pathogenesis of MASH involves genetic factors and gut microbiota alteration, yet the role of host-microbe interactions in MASH development remains unclear. Here, we discover that mice with intestinal epithelial cell-specific knockout of Tm6sf2 (Tm6sf2^ΔIEC) develop MASH, accompanied by impaired intestinal barrier and microbial dysbiosis. Transplanting stools from Tm6sf2^ΔIEC mice induces steatohepatitis in germ-free recipient mice, whereas MASH is alleviated in Tm6sf2^ΔIEC mice co-housed with wild-type mice. Mechanistically, Tm6sf2-

SUBMITTER: Zhang X 

PROVIDER: S-EPMC11774752 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature