Research Article Details
| Article ID: | A12836 |
| PMID: | 30261661 |
| Source: | Int J Mol Sci |
| Title: | Fc Gamma Receptor IIb Expressed in Hepatocytes Promotes Lipid Accumulation and Gluconeogenesis. |
| Abstract: | 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 (FcγRIIb) and its ligand are reported to be associated with obesity and type 2 diabetes mellitus (T2DM). As knowledge about FcγRIIb in the literature is mostly generated from studies on skeletal muscle tissue, the expression and function of FcγRIIb in the liver and hepatocytes are largely unknown. In this study, we identified the expression of FcγRIIb in primary cultured mouse hepatocytes: FcγRIIb was upregulated in response to oleic acid (OA) in a dose dependent manner. FcγRIIb knockdown using shRNA suppressed the lipid and triglyceride accumulation, and mRNA expression of ACC1, FASn, CD36, MTTP, and ApoB in OA-treated HepG2 cells. FcγRIIb 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, FcγRIIb hindered insulin-induced phosphorylation of AKT and FOXO1, and in turn upregulated G6Pase and PEPCK mRNA expression, suggesting that FcγRIIb promotes gluconeogenesis by suppressing the AKT/FOXO1/G6Pase/PEPCK pathway in hepatocytes. This study reveals a novel role for FcγRIIb in regulating lipid metabolism and glycometabolism, and provides a new therapeutic target to improve NAFLD. |
| DOI: | 10.3390/ijms19102932 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |