Induction of adiponectin in skeletal muscle of type 2 diabetic mice: in vivo and in vitro studies

Aims/hypothesis: Adiponectin is an adipokine that exhibits insulin-sensitising, fat-burning and anti-inflammatory properties as well as modulatory effects on oxidative stress. We examined whether adiponectin could be induced in a non-adipose tissue, skeletal muscle, in response to metabolic or oxidative aggression both in vivo (in a murine model of type 2 diabetes) and in vitro. Methods: Obese and diabetic ob/ob mice were used and compared with lean littermates. Some obese mice were treated with the antioxidant probucol for 3 weeks. At the end of the experiment, blood was sampled and tibialis anterior muscles were collected for mRNA measurement and immunohistochemistry. Additional in vitro experiments were performed on C2C12 myotubes cultured for up to 48 h. Results: In spite of hypoadiponectinaemia, Adipoq mRNA levels were markedly increased in the skeletal muscle of ob/ob mice and correlated with systemic oxidative stress. Adipoq upregulation was shown in laser-microdissected myocytes of obese mice. Concomitantly, immunoreactivity for adiponectin was enhanced in obese muscle fibres together with lipid infiltration and local markers of oxidative stress. In cultured C2C12 myotubes, a triglyceride mix and reactive oxygen species producers (H2O2 or a lipoperoxidation end-product) upregulated Adipoq expression and adiponectin production. This effect was reversed by an antioxidant. Finally, treatment of obese mice with probucol also attenuated upregulation in muscle. Conclusions/interpretation: The paradoxical upregulation of adiponectin in muscle of obese and diabetic mice may result from lipotoxicity and related oxidative stress. This unexpected finding could be viewed as a local protection to counteract ectopic fat deposition and oxidative damage.