Role of fibroblast growth factor-21 in glucose-lipid metabolism in mice adipocyte and hepatocyte / 中华内分泌代谢杂志

ABSTRACT

Objective To investigate the role played by fibroblast growth factor-21 (FGF-21) in glucoselipid metabolism in mice adipocyte and hepatocyte. Methods FGF-21 over-expressive vector and FGF-21-shRNA vector were transfected to Hepa1-6 hepatocyte and 3T3-L1 adipocyte, respectively. FGF-21 protein levels were evaluated by Western blotting, glucose uptake rate (GUR) was evaluated by radioimmunoassay. The mRNA expression of transcription factors was detected by real-time quantitative PCR. Results Transfection of pcDNAFGF21 significantly increased FGF-21 expression in both liver and fat cells (4.8 fold and 4.2 fold, both P<0.05). Moreover, FGF-21 expressions were down-regulated by 86. 3% and 77. 8% with pGenesil-FGF21,respectively (both P<0.05 ). The FGF-21 up-regulation markedly increased GUR and decreased intracellular triglycerides content in the 3T3-L1 adipocyte. Meanwhile, the up-regulation of glucose transporter-1, insulin receptor substrate-1 (IRS-1), PPARγ, adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL),and adipocyte fatty acid binding protein 2 ( ap2 ) mRNA expressions were also observed ( all P<0. 05 ). The reverse changes happened in FGF-21 deficient adipocyte except IRS-1. In hepatocyte, FGF-21 has no effect on GUR.FGF-21 over-expression reduced PPARγ, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), and phosphoenolpyruvate carboxykinase (PEPCK) mRNA expressions, and increased low-density lipoprotein receptor expression (P<0.05). Conclusions FGF-21 regulates glucose homeostasis and accommodates intracellular fat content in adipocyte. In hepatocyte, FGF-21 plays an important role in gluconeogenesis and cholesterol metabolism.