Regulation of uncoupling protein-2 and uncoupling protein-3 mRNA expression during lipid infusion in human skeletal muscle and subcutaneous adipose tissue

To study the effect of nonesterified fatty acids (NEFAs) on uncoupling prot ein-2 (UCP-2) and uncoupling protein-3 (UCP-3) gene expression, a triglycer ide emulsion was infused for 5 h in 14 healthy volunteers. A euglycemic-hyp erinsulinemic clamp was administered concomitantly in 7 of the 14 subjects. The mRNA levels of UCP-2 and of the short (UCP-3S) and long (UCP-3L) isofo rms of UCP-3 were quantified by reverse transcription-competitive polymeras e chain reaction in tissue biopsies taken before and at the end of the infu sion periods. Plasma NEFA concentrations increased from 362 +/- 52 to 989 /- 157 mu mol/l (P = 0.018) during triglyceride infusion. UCP-3L (8 +/- 1 v s. 19 +/- 2 amol/mu g total RNA, P = 0.018) and UCP-3S (11 +/- 2 vs. 17 +/- 3 amol/mu g total RNA, P = 0.027) mRNA levels increased in skeletal muscle during triglyceride infusion. UCP-3L mRNA levels were positively correlate d with plasma NEFA concentrations (r = 0.53, P = 0.005) and with lipid oxid ation rates (r = 0.56, P = 0.004) determined by indirect calorimetry In con trast, the expression of UCP-2 was not affected by lipid infusion in skelet al muscle or in subcutaneous adipose tissue. During the hyperinsulinemic cl amp (plasma insulin concentrations 202 +/- 12 pmol/l), NEFA levels (405 +/- 49 vs. 648 +/- 77 mu mol/l, P = 0.063) and lipid oxidation rates (0.67 +/- 0.09 vs. 0.84 +/- 0.10 mg . kg(-1) . min(-1), P = 0.091) were not signific antly increased during triglyceride infusion. Under such conditions, the in duction of UCP-3L and UCP-3S mRNA expression was totally prevented (8 +/- 2 vs. 8 +/- 1 and 8 +/- 2 vs. 9 +/- 2 amol/mu g total RNA, respectively). We conclude that increased plasma NEFA levels by lipid infusion for 5 h induc es the expression of UCP-3 but not UCP-2 in humans. During triglyceride inf usion, physiological hyperinsulinemia appears to prevent the induction of U CP-3 mRNA levels.