| First Author | Pinanga YD | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 9 | Pages | 107625 |
| PubMed ID | 37670786 | Mgi Jnum | J:340588 |
| Mgi Id | MGI:7528348 | Doi | 10.1016/j.isci.2023.107625 |
| Citation | Pinanga YD, et al. (2023) TM4SF5-mediated abnormal food-intake behavior and apelin expression facilitate non-alcoholic fatty liver disease features. iScience 26(9):107625 |
| abstractText | Transmembrane 4 L six family member 5 (TM4SF5) engages in non-alcoholic steatohepatitis (NASH), although its mechanistic roles are unclear. Genetically engineered Tm4sf5 mice fed ad libitum normal chow or high-fat diet for either an entire day or a daytime-feeding (DF) pattern were analyzed for metabolic parameters. Compared to wild-type and Tm4sf5(-/-) knockout mice, hepatocyte-specific TM4SF5-overexpressing Alb-TG(Tm4sf5-Flag) (TG) mice showed abnormal food-intake behavior during the mouse-inactive daytime, increased apelin expression, increased food intake, and higher levels of NASH features. DF or exogenous apelin injection of TG mice caused severe hepatic pathology. TM4SF5-mediated abnormal food intake was correlated with peroxisomal beta-oxidation, mTOR activation, and autophagy inhibition, with triggering NASH phenotypes. Non-alcoholic fatty liver disease (NAFLD) patients' samples revealed a correlation between serum apelin and NAFLD activity score. Altogether, these observations suggest that hepatic TM4SF5 may cause abnormal food-intake behaviors to trigger steatohepatitic features via the regulation of peroxisomal beta-oxidation, mTOR, and autophagy. |
