Effects of enhanced muscle growth by myostatin propeptide trangene and dietary fat content on gene expression of adiponectin, adiponectin receptors, PPAR-alpha and PPAR-beta

Thesis (M.S.)--University of Hawaii at Manoa, 2007.Includes bibliographical references (leaves 70-81).vii, 86 leaves, bound ill. (some col.) 29 cmMyostatin, a member of the transforming growth factor-β superfamily, is a highly conserved negative regulator of muscle growth which undergoes post-translational modification to yield the active form. We have demonstrated that transgenic over-expression of myostatin propeptide dramatically enhanced skeletal muscle development and decreased fat mass. By feeding the transgenic mice either a high-fat diet or normal fat diet we found that transgenic, high-fat diet mice had improved insulin sensitivity, normal fat deposition, enhanced muscle growth, and significantly higher levels of circulating adiponectin compared to wild-type mice. Adiponectin is known to ameliorate insulin resistance and increase fatty acid oxidation. We theorized that the interaction between high-fat diet and myostatin propeptide would increase adiponectin mRNA expression in fat tissue depots and corresponding adiponectin receptor mRNA expression in muscle and liver. Results from real-time PCR analysis indicated transgenic mice fed a high-fat diet displayed increased adiponectin mRNA expression in epididymal fat by 2- fold over wild-type littermates. These mice also displayed increased expression of PPAR-α and PPAR-β above the other three groups in epididymal fat. The wild-type mice fed a normal-fat diet expressed the most AdipoR1 and R2 in liver tissue, 1.03-fold and 1.32- fold over the other groups, respectively. The transgenic mice fed a high-fat diet did not show increased mRNA level of either receptor in muscle or liver tissue. The increase in expression of adiponectin mRNA may partially explain why the high-fat diet did not cause obesity and insulin resistance in transgenic mice