[Regulation of hepatic lipid metabolism by adiponectin via IRS-2 phosphorylation in OLETF rats].

Objective To explore the effect and mechanism of adiponectin on hepatic lipid metabolism in Otsuka Long Evans Tokushima fatty (OLETF) rats.Methods Twenty male OLETF rats and 10 male Long-Evans Tokushima (LETO) rats were sacrificed at 8,32 or 40-week old to examine the fasting blood glucose,plasm insulin,adiponectin and blood lipid profile.The levels of triglyceride,cholesterol,adiponectin,phosphotyrosine of IRS-2,acetyl-coenzyme A carboxylase and sterol regulatory element-binding protein 1 (SREBP-1) mRNA in liver tissue were determined by chemical enzymatic assay,enzyme-linked immunosorbent assay (ELISA) or Western blot.Results Higher insulin level,lower insulin sensitivity index and deteriorated lipid metabolism was observed in OLETF rats since 32-week age. ACC (acetyl coenzyme A carboxylase) and SREBP-1 mRNA expression,lowered plasma adiponectin (OLETF vs LETO:8weeksage,2.38±0.23 vs3.1 ±0.17,P＜0.05; 32 weeks age,1.51±0.05 vs2.M±0.34,P＜0.01; 40 weeks age,1.24±0.04 vs 2.64 ±0.49 ng/ml,P＜0.01) and liver tissue (8,32 or40 weeksage,2.24±0.18 vs 2.68 ±0.13,2.04±0.19 vs 2.51 ±0.14,1.76±0.12 vs 2.47 ±0.21 μg/grespectively,P ＜ 0.05) as well as elevated triglyceride (TG) (40 weeks age,TG 1.88 ± 0.11 vs 0.51 ±0.07 mmol/L,P ＜ 0.01 ) and cholesterol (40 weeks age,total cholesterol 0.94 ± 0.17 vs 0.69 ± 0.14mmol/L,P ＜0.01 ) and lowered IRS-1 ( insulin receptor substrate 1 ) tyrosin phosphorylation in liver tissue in OLETF rats were observed.The hepatic adiponectin was positively correlated with the level of py-IRS2 and inversely with those of hepatic ACC,SREBP-1 mRNA,triglyceride and cholesterol ( r =- 0.431,- 0.396,-0.353,-0.349,P ＜0.05).Conclusion Adiponectin may affect the signaling pathway of hepatic insulin via tyrosin phosphorylation of IRS-2.It is involved in the regulation of hepatic lipid metabolism. Key words: Diabetes mellitus;  Adiponectin;  Insulin receptor substrate-2;  Lipid metabolism