title: [Regulation of hepatic lipid metabolism by adiponectin via IRS-2 phosphorylation in OLETF rats].
abstract: 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, plasma 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: 8 weeks age, 2.38 ± 0.23 vs 3.1 ± 0.17, P < 0.05; 32 weeks age, 1.51 ± 0.05 vs 2.84 ± 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 or 40 weeks age, 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/g respectively, 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 ± 0.14 mmol/L, P < 0.01) and lowered IRS-1 (insulin receptor substrate 1) tyrosine 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).
  
  
  CONCLUSIONS
  Adiponectin may affect the signaling pathway of hepatic insulin via tyrosine phosphorylation of IRS-2. It is involved in the regulation of hepatic lipid metabolism.
authors.affiliation: Department of Endocrinology & Metabolism, Southern Medical University, Guangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
authors.forename: Chen-zhong
authors.initials: CZ
authors.lastname: Li
authors.forename: Yong-hua
authors.initials: YH
authors.lastname: Pan
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan-mei
authors.initials: YM
authors.lastname: Zeng
authors.forename: Yao-ming
authors.initials: YM
authors.lastname: Xue
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000818:Animals; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D020334:Rats, Inbred OLETF
chemical_list: D052242:Adiponectin; D055504:Insulin Receptor Substrate Proteins; C526299:Irs2 protein, rat