All ETDs from UAB

Advisory Committee Chair

Qinglin Yang

Advisory Committee Members

Amanda Brown

Pi-Ling Chang

Document Type

Thesis

Date of Award

2012

Degree Name by School

Master of Science (MS) School of Health Professions

Abstract

Liver X receptors (LXRs) are important regulators of cholesterol, fatty acid, and glucose homeostasis. Many researchs focus on the liver, but tissue-specific roles of LXRs in other tissues remain elusive. Based on in vitro studies on cultured cells, the roles of LXRs in skeletal muscle have been proposed. Nevertheless, the in vivo roles of LXRs in skeletal muscle remain lacking. Skeletal muscle is an important insulin targeting tissue, which plays a key role in regulating insulin sensitivity. Abnormal lipid metabolism and homeostasis have been demonstrated to play a crucial role in the development of insulin resistance in skeletal muscle. To understand the tissue-specific role of LXR in regulating metabolism in skeletal muscle, and subsequently insulin sensitivity, a skeletal muscle-specific LXR knockout mouse model was generated. Strikingly, we observed that these mice were susceptible to diet induced insulin resistance. Recent reports suggest that LXR deficiency related metabolic disorder may play a crucial role in the exacerbated diet-induced insulin resistance. Further study on lipid content revealed that under chow diet, skeletal muscle LXR deficiency mice showed no sigificant diference in body weight and body composition, compared to control groups. However, under high-fat diet, skeletal muscle LXR deficiency mice showed increased body weight and fat mass, decreased lean mass and altered lipid content (increased triglyceride, free cholesterol and decreased NEFA level in skeletal muscle, with increased NEFA in plasma). Taken together with the observed impaired insulin sensitivity, the abnormal lipid homeostasis may be attributed to LXR deficiency related lipid and cholesterol metabolic disorders and to insulin resistance in skeletal muscle LXRdeficiency mice. Therefore, skeletal muscle LXR is a potential therapeutic target for insulin resistance and diabetes.

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