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Mechanisms of Adiponectin Resistance and the Consequences of Adiponectin Deficiency in Exercise Training

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Title: Mechanisms of Adiponectin Resistance and the Consequences of Adiponectin Deficiency in Exercise Training
Author: Ritchie, Ian
Department: Department of Human Health and Nutritional Sciences
Program: Human Health and Nutritional Sciences
Advisor: Dyck, David
Abstract: This thesis examined whether rapid shifts in skeletal muscle redox balance that follow a high fat diet impair adiponectin (Ad) stimulated fatty acid (FA) oxidation in skeletal muscle from rats. This thesis also examined the importance of Ad as a regulator of mitochondrial content in skeletal muscle at rest and following exercise training. Lastly, this thesis examined whether Ad is required for the increased insulin response observed following exercise training A high fat diet rapidly impairs the ability of Ad to increase FA oxidation in skeletal muscle, but the underlying mechanisms are unknown. In the first study the capacity of Ad to increase palmitate oxidation in soleus and extensor digitorum longus (EDL) was attenuated with HF feeding. HF feeding decreased total GSH and GSH/2GSSG in soleus, but not EDL. N-acetylcysteine prevented the reductions in GSH and GSH/2GSSG in soleus, but did not preserve Ad response. Therefore our data indicates that Ad resistance is induced in both oxidative and glycolytic skeletal muscle, independently of altered cellular redox state. The second study examined the role of Ad as a regulator of mitochondrial content using Ad knockout (AdKO) mice. There were no differences in mitochondrial protein content in red and white gastrocnemius (RG, WG) between WT and AdKO animals. Acute exercise increased the phosphorylation of AMPK and the mRNA expression of mitochondrial proteins in RG and WG with no differences between genotypes. Finally, 8 weeks of exercise training increased the protein content of mitochondrial markers similarly in muscle from both WT and AdKO mice. We conclude that Ad is not required for the regulation of mitochondrial content at rest or during exercise training. In the third study, 8 weeks of exercise training significantly increased glucose and insulin tolerance in both WT and AdKO mice. There were no differences in glucose tolerance between genotypes but insulin tolerance was improved to a greater extent in AdKO mice. There were no genotype differences in the insulin-stimulated phosphorylation of AKT or AS160 in RG or WG. Our results indicate the presence of Ad is not required for exercise-induced increases in insulin response.
URI: http://hdl.handle.net/10214/8309
Date: 2014-08


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