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The development of high fat diet induced adiponectin resistance in rodent skeletal muscle

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Title: The development of high fat diet induced adiponectin resistance in rodent skeletal muscle
Author: Mullen, Kerry Lynn
Department: Department of Human Biology and Nutritional Sciences
Advisor: Dyck, David J.
Abstract: Adiponectin (Ad) is an insulin-sensitizing adipokine, attributable in part to its ability to stimulate skeletal muscle fatty acid (FA) oxidation and prevent intramuscular lipid accumulation and associated lipotoxicity. In established cases of obesity and insulin resistance (IR), resistance to this insulin-sensitizing adipokine has been shown. However, whether a high fat diet, a known contributor to obesity and IR can induce Ad resistance is unknown. Furthermore, whether the type of fat in the diet influences the development of Ad resistance and whether this resistance precedes and contributes to the development of IR is unknown. Finally, the cause of Ad resistance is unknown. It was hypothesized that a high fat diet would induce skeletal muscle Ad resistance by triggering inflammation and this would occur prior to the onset and development of IR. It was also hypothesized that a diet high in saturated fat (SAT) would cause faster changes than a diet high in polyunsaturated fat (PUFA). From the work presented herein, several novel findings have been made. Importantly, skeletal muscle Ad resistance can be induced by high fat feeding in rats. This resistance is defined as an inability of globular adiponectin (gAd) to acutely stimulate FA oxidation and phosphorylate acetyl CoA carboxylase (ACC) in oxidative soleus muscle. However, the type of FA in the diet is important in this development. While both PUFA and SAT FA can induce Ad resistance, the induction is more rapid following a SAT diet, occurring within 3 days, while evidence of Ad resistance following a PUPA diet is not apparent until 4 weeks. Critical to note is that SAT FA-induced Ad resistance develops prior to accumulation of intramuscular DAG and ceramide, increased FA transporter content at the plasma membrane and impaired maximally insulin-stimulated glucose uptake. Finally, the underlying cause of Ad resistance remains to be fully elucidated. A change in absolute or phosphorylated inflammatory proteins or total SOCS-3 content in skeletal muscle does not explain the observed development of Ad resistance. Together, this data suggests that Ad resistance may be an important step in the pathogenesis of IR and its cause warrants further investigation.
Date: 2010
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