Metabolic and anthropometric factors related to skeletal muscle UCP3 gene expression in healthy human adults

Abstract

This cross-sectional investigation sought to determine the relationship between selected metabolic, endocrine, and anthropometric factors and skeletal muscle UCP3 mRNA in healthy adult humans. Twenty-four healthy adults (13 male and 11 female) across a range of aerobic capacity, age, and body composition were studied. Muscle biopsies were obtained from the vastus lateralis, from which UCP3 mRNA was quantified by Northern blot, and fiber type was determined by use of the myosin ATPase staining procedure. In addition, resting energy expenditure and maximum rate of oxygen consumption were determined by indirect calorimetry, body composition was determined by dual-energy X-ray absorptiometry, and fasting plasma leptin and insulin were determined by ELISA. UCP3 mRNA was correlated positively with the percent type I fibers (r ϭ 0.842, P Ͻ 0.001), plasma leptin (r ϭ 0.454, P ϭ 0.026), and plasma insulin (r ϭ 0.615, P Ͻ 0.001) and inversely to age (r ϭ Ϫ0.411, P ϭ 0.046). Stepwise multiple regression analysis determined that percent type I muscle fibers was the best predictor of vastus lateralis UCP3 mRNA, and no other variable entered the equation (model r 2 ϭ 0.66). This study suggests that of the variables measured, UCP3 mRNA is primarily related to skeletal muscle fiber type in healthy adults. The factors that contribute to fiber-specific differences in UCP3 mRNA expression will need to be examined in future studies. uncoupling proteins; leptin; metabolic rate THE FACTOR(S) THAT CONTRIBUTE to the interindividual variability in resting metabolic rate have been the subject of intense research interest (38,44,54). The recent cloning of novel uncoupling protein isoforms (UCP2 and UCP3) has stimulated interest in potential molecular mediators of the variability in metabolic rate and susceptibility to obesity (8,13,15). The canonical UCP isoform (UCP1) is well accepted to act as an uncoupler of electron transport and oxidative phosphorylation in brown adipose tissue (BAT), resulting in the regulated production of heat (11,25). In contrast, there is considerable debate about whether the novel UCPs are truly uncouplers in vivo, and the specific physiological role of UCP2 and UCP3 in skeletal muscle remains to be elucidated (33). There is evidence indicating that UCP2 and UCP3 function similarly to UCP1 in dissipating the proton gradient of the inner mitochondrial membrane during oxidative respiration (8,13,15,17). It is intuitive then to investigate the relationship between the expression of these novel proteins and other variables known to be associated with metabolism.Studies aimed at understanding the regulation of UCP3 gene expression have demonstrated tissue-specific responses to perturbations designed or "hypothesized" to alter UCP3 gene regulation. The expression and regulation of UCP3 in skeletal muscle are of considerable interest because of the large mass of this organ and its well-documented contribution to both basal metabolism (40) and basal proton leak (39). UCP2 is speculated to function similarly to UCP3; ho...

Effect of 48-h Food Deprivation on the Expressions of Myosin Heavy-Chain Isoforms and Fiber Type-Related Factors in Rats

“…UCP3 is expressed mainly in the skeletal muscle, and is thought to play an important role in thermogenesis in larger mammals, including humans. The UCP3 mRNA shows a significant positive correlation with the percentage of type 1 fibers in healthy adult humans (22 crons and very low density lipoproteins, representing the rate-limiting step in the utilization of triglyceridederived fatty acids (10). LPL activity in slow fibers was approximately 14-to 20-fold higher than that in fast fibers (23).…”