Zhu Bo, Li Chen-zhong, Pan Yong-hua, Zhang Yan, Zeng Yan-mei, Xue Yao-ming
Department of Endocrinology & Metabolism, Southern Medical University, Guangzhou, China.
Zhonghua Yi Xue Za Zhi. 2011 Nov 29;91(44):3134-8.
To explore the effect and mechanism of adiponectin on hepatic lipid metabolism in Otsuka Long Evans Tokushima fatty (OLETF) rats.
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.
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).
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.
探讨脂联素对大冢长-艾氏-德岛肥胖（OLETF）大鼠肝脏脂质代谢的影响及其机制。
将20只雄性OLETF大鼠和10只雄性长-艾氏-德岛（LETO）大鼠在8周、32周或40周龄时处死，检测空腹血糖、血浆胰岛素、脂联素和血脂谱。采用化学酶法、酶联免疫吸附测定（ELISA）或蛋白质免疫印迹法测定肝组织中甘油三酯、胆固醇、脂联素、胰岛素受体底物-2（IRS-2）的磷酸酪氨酸、乙酰辅酶A羧化酶和固醇调节元件结合蛋白1（SREBP-1）mRNA的水平。
自32周龄起，OLETF大鼠出现胰岛素水平升高、胰岛素敏感性指数降低和脂质代谢恶化。观察到OLETF大鼠肝组织中乙酰辅酶A羧化酶（ACC）和SREBP-1 mRNA表达增加，血浆脂联素降低（OLETF与LETO比较：8周龄时，2.38±0.23对3.1±0.17，P<0.05；32周龄时，1.51±0.05对2.84±0.34，P<0.01；40周龄时，1.24±0.04对2.64±0.49 ng/ml，P<0.01）以及肝脏组织中脂联素降低（8周、32周或40周龄时，分别为2.24±0.18对2.68±0.13、2.04±0.19对2.51±0.14、1.76±0.12对2.47±0.21 μg/g，P<0.05），同时甘油三酯（TG）升高（40周龄时，TG 1.88±0.11对0.51±0.07 mmol/L，P<0.01）和胆固醇升高（40周龄时，总胆固醇0.94±0.17对0.69±0.14 mmol/L，P<0.01），且肝脏组织中IRS-1（胰岛素受体底物1）酪氨酸磷酸化降低。肝脏脂联素与磷酸化IRS2水平呈正相关，与肝脏ACC、SREBP-1 mRNA、甘油三酯和胆固醇水平呈负相关（r=-0.431、-0.396、-0.353、-0.349，P<0.05）。
脂联素可能通过IRS-2的酪氨酸磷酸化影响肝脏胰岛素信号通路，参与肝脏脂质代谢的调节。
