| Adiponectin was first identified as an adipokine exclusively derived from adipose tissue and then characterized as an anti-diabetic adipokine via its insulin-like and insulin-sensitizing effects. However, the underlying molecular mechanisms for these beneficial metabolic effects still remain to be fully understood. In obesity and diabetes, a decreased circulating level of adiponectin, particularly the HMW form of adiponectin was observed and correlated tightly with metabolic syndrome. In this thesis, I investigated regulation of skeletal muscle metabolism by adiponectin and the mechanisms responsible by performing cell, animal and human studies.;Study 2: Adiponectin can protect and correct insulin resistance in skeletal muscle induced by various high fat diet feeding period and improve whole body glucose homeostasis via its ability to correct anti-oxidative defense systems and improve mitochondrial function. This study further confirms the therapeutic value of adiponectin for the treatment of obesity related insulin resistance.;Study 3: In a study of individuals with or without metabolic syndrome, HMW adiponectin (but not hexameric or trimeric) tracks closely with various characteristics of the metabolic syndrome. In particular, a strong independent inverse association exists between ALT and HMW adiponectin.;In summary, my study demonstrated that adiponectin is a potent insulin sensitizer. It can act as an adipokine or myokine to enhance whole body insulin sensitivity and its effects in skeletal muscle occur via anti-oxidative effects and improved mitochondrial function. The improved insulin sensitivity and metabolic flexibility contribute toward restored energy homeostasis.;Study 1: I demonstrate the ability of skeletal muscle cells to produce adiponectin which can mediate autocrine metabolic effects, thus establishing adiponectin as a bona fide myokine. Furthermore, skeletal muscle adiponectin production is altered in animal models of obesity and diabetes and these changes can be corrected by the anti-diabetic drug rosiglitazone. |
