The fat-derived hormone adiponectin reverses insulin resistance associatedwith both lipoatrophy and obesity

Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we s how that decreased expression of adiponectin correlates with insulin resist ance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver i n obese mice. This effect results from increased expression of molecules in volved in both fatty-acid combustion and energy dissipation in muscle. More over, insulin resistance in lipoatrophic mice was completely reversed by th e combination of physiological doses of adiponectin and leptin, but only pa rtially by either adiponectin or leptin alone. We conclude that decreased a diponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the r eplenishment of adiponectin might provide a novel treatment modality for in sulin resistance and type 2 diabetes.