The pathophysiological roles of adiponectin in the regulation of type 2 diabetes, hyperlipidemia and atherosclerosis

点击翻译按钮获取中文摘要

Obesity-linked diseases such as diabetes and cardiovascular disease are sharply increasing in developed and developing countries. Heterozygous PPARg or CBP knockout mice were protected from high-fat diet induced obesity and insulin resistance (Mol.Cell 4:597, 1999; Nature Genetics 30:221, 2002). We then carried out systematic gene profiling analysis of these mice and found that adiponectin/Acrp30 was overexpressed. Functional analyses including generation of adiponectin transgenic or knockout mice have revealed that adiponectin serves as an insulin sensitizing adipokine (Nature Medicine 7:941, 2001). In fact, obesity-linked down regulation of adiponectin was a mechanism whereby obesity can cause insulin resistance and diabetes. We further studied the mechanism of adiponectin action and found that adiponectin can activate AMP kinase pathway and PPARa pathway, leading to fat combustion and amelioration of insulin resistance (Nature Medicine 8:1288, 2002). Recently, we have cloned adiponectin receptors in the skeletal muscle (AdipoR1) and liver (AdipoR2), which appear to comprise a novel cell surface receptor family (Nature 423:762, 2003). The expression of AdipoR1/R2 appears to be regulated by several physiological and pathophysiological states such as, fasting/refeeding and hyperinsulinemia, and correlated with adiponectin sensitivity (J.Biol.Chem. published on line on Apr 29, 2004). Adiponectin receptor agonists and adiponectin sensitizers should serve as versatile treatment strategies for obesity linked diseases such as diabetes.