EXPRESSION OF MESSENGER-RNAS ENCODING UNCOUPLING PROTEINS IN HUMAN SKELETAL-MUSCLE - EFFECTS OF OBESITY AND DIABETES

To explore the potential role of the uncoupling protein (UCP) family i n human obesity and diabetes, we have used the reverse transcription-p olymerase chain reaction to quantify UCP mRNA expression in human skel etal muscle. Levels of mRNA for UCP2, and for both short (UCP3S) and l ong (UCP3L) forms of UCP3, were highly correlated in individuals, indi cating that gene transcription of these UCPs may be coordinately regul ated by common mechanisms. In normal glucose-tolerant individuals, mus cle UCP2 mRNA levels mere positively correlated with percentage of bod y fat and with BMI (r = 0.6 and P < 0.05 for both). UCP3S mRNA levels were also positively correlated with percentage of body fat (r = 0.52, P < 0.05), and UCP3L mRNA tended to increase as a function of obesity (0.05 < P < 0.1). UCP mRNA levels, however were not correlated with r esting metabolic rate. UCP3S and UCP3L mRNA levels (P < 0.05) and the UCP2 mRNA level (P = 0.09) were increased by 1.8- to 2.7-fold in type 2 diabetes, an effect that could not be explained by obesity. No signi ficant difference was found for UCP2, UCP3S, or UCP3L mRNA levels betw een insulin-sensitive and insulin-resistant nondiabetic subgroups. We conclude that 1) skeletal muscle mRNA levels encoding UCP2 and UCP3 ar e correlated among individuals and may be coordinately regulated; 2) U CP3 expression is not regulated by differential effects on UCP3L and U CP3S forms of the mRNA; and 3) UCP mRNA expression tends to increase i n muscle as a function of obesity but not of resting metabolic rate or insulin resistance, and is increased in patients with type 2 diabetes .