All ETDs from UAB

Advisory Committee Chair

W Timothy Garvey

Advisory Committee Members

Yuchang Fu

Gary R Hunter

Timothy R Nagy

Qinglin Yang

Document Type

Dissertation

Date of Award

2011

Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions

Abstract

Nuclear receptor NR4A3 (NOR-1, MINOR) mediates transcriptional responses to ß-adrenergic signaling, is increased in insulin sensitive mice and humans, and enhances insulin-stimulated glucose transport in cultured adipocytes and myocytes. We therefore sought to determine the role of NR4A3 in in vivo adipose tissue and skeletal muscle physiology. Following adipose-specific NR4A3 over-expression in mice, we observed reduced circulating epinephrine due to enhanced catabolism of catecholamines in adipose tissue. Furthermore, this reduction in circulating epinephrine produced broad physiological consequences, including poor glucose tolerance, reduced insulin sensitivity, dyslipidemia, poor cardiac function, and behavioral alterations. In skeletal muscle, we show that NR4A3 protein associates with exercise, age, and insulin sensitivity, but not with high fat diet in mice or percent trunk fat in humans. We also show a positive correlation between NR4A3 and % type I muscle fibers and a negative correlation between NR4A3 and % type IIa muscle fibers. Lastly, we demonstrate positive correlations between NR4A3 protein and myostatin protein in both mouse and skeletal muscle, indicating that NR4A3 as an activator of myostatin expression may drive myocytes to an oxidative phenotype by suppressing genes associated with glycolytic fibers.

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