| First Author | Shu T | Year | 2018 |
| Journal | Int J Mol Sci | Volume | 19 |
| Issue | 10 | PubMed ID | 30261661 |
| Mgi Jnum | J:341457 | Mgi Id | MGI:6856349 |
| Doi | 10.3390/ijms19102932 | Citation | Shu T, et al. (2018) Fc Gamma Receptor IIb Expressed in Hepatocytes Promotes Lipid Accumulation and Gluconeogenesis. Int J Mol Sci 19(10):2932 |
| abstractText | Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic lipid accumulation in the liver, usually combined with hepatic insulin resistance. Fc-gamma receptor-IIb (FcgammaRIIb) and its ligand are reported to be associated with obesity and type 2 diabetes mellitus (T2DM). As knowledge about FcgammaRIIb in the literature is mostly generated from studies on skeletal muscle tissue, the expression and function of FcgammaRIIb in the liver and hepatocytes are largely unknown. In this study, we identified the expression of FcgammaRIIb in primary cultured mouse hepatocytes: FcgammaRIIb was upregulated in response to oleic acid (OA) in a dose dependent manner. FcgammaRIIb knockdown using shRNA suppressed the lipid and triglyceride accumulation, and mRNA expression of ACC1, FASn, CD36, MTTP, and ApoB in OA-treated HepG2 cells. FcgammaRIIb deficiency mice fed with high fat diet (HFD) had significantly lower liver weight and liver to body weight ratio, as well as less triglyceride accumulation in the livers. In glycometabolism, FcgammaRIIb hindered insulin-induced phosphorylation of AKT and FOXO1, and in turn upregulated G6Pase and PEPCK mRNA expression, suggesting that FcgammaRIIb promotes gluconeogenesis by suppressing the AKT/FOXO1/G6Pase/PEPCK pathway in hepatocytes. This study reveals a novel role for FcgammaRIIb in regulating lipid metabolism and glycometabolism, and provides a new therapeutic target to improve NAFLD. |
