TM4SF5-mediated abnormal food-intake behavior and apelin expression facilitate non-alcoholic fatty liver disease features
- 주제(키워드) Biological sciences , Cell biology , Molecular biology , Physiology
- 등재 SCIE, SCOPUS
- OA유형 All Open Access; Gold Open Access; Green Open Access
- 발행기관 Elsevier Inc.
- 발행년도 2023
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000211768
- 본문언어 영어
- Published As https://doi.org/10.1016/j.isci.2023.107625
초록/요약
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-TGTm4sf5−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 β-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 β-oxidation, mTOR, and autophagy. © 2023 The Author(s)
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