Uncoupling protein-2 and-3 messenger ribonucleic acids in adipose tissue and skeletal muscle of healthy males: Variability, factors affecting expression, and relation to measures of metabolic rate

Mitochondrial uncoupling protein-a and -3 (UCP2 and UCP3) may be involved i n the modulation of resting metabolic rate and energy balance. To investiga te their variability, the influence of this on the variability of energy ex penditure, and potential regulatory factors of the expression of the corres ponding genes, we measured their messenger ribonucleic acids (mRNAs) in mus cle and white adipose tissue of lean, healthy men and correlated the abunda nce of these mRNAs (attomoles per mu g total RNA) with measures of resting metabolic rate, hormone levels (thyroid hormones, insulin, glucagon, leptin , and catecholamines), and fuels potentially involved in energy balance reg ulation. We also investigated whether the thiazolidinedione, troglitazone, stimulates UCP2 and UCP3 mRNA levels to follow up on the observation that t his antidiabetic drug increases the levels of expression in cultured cells. We found UCP2 and UCP3 mRNA levels to be highly variable and poorly correl ated with measures of energy expenditure and with most factors affecting en ergy balance; Only nocturnal urinary norepinephrine excretion could explain a significant fraction of the variability in both UCP2 and UCP3 expression in muscle, but not adipose tissue. Thyroid hormone and norepinephrine excr etion were found to contribute to the variability of resting metabolic rate , but this could not be explained by an effect on UCP mRNAs. Troglitazone a ffected neither the expression of UCPs nor the hormones or the measures of metabolic rate investigated. In conclusion, our results show that the expre ssion of UCP2 and UCP3 genes is quite variable in healthy males and that th is variability does not explain that in resting energy expenditure, and sug gest that sympathetic activity is an important potential regulator of the e xpression of these proteins in skeletal muscle. However, the data do not su pport the concept that regulation of the expression of these genes is the m ost important level of control of UCP3 and UCPB functions, and other levels of control have to be invoked.