Regulation of uncoupling protein-2 and-3 by growth hormone in skeletal muscle and adipose tissue in growth hormone-deficient adults

The newly described uncoupling proteins, UCP2 and UCP3, may play a role in regulating energy expenditure (EE) in humans. GH deficiency (GHD) is associ ated with decreased lean body mass, increased adiposity, and reduced EE, wh ich are reversed by GH treatment. In the present study we investigated whet her GH treatment for 4 months influenced the expression of UCPs in skeletal muscle and adipose tissue in 22 GHD patients who were investigated before and after GH (n = 11) or placebo (n = II) treatment. GH treatment increased the amount of lean body mass by 4.5% (P < 0.05) and decreased body fat mas s by 12% (P < 0.05), whereas no changes in these parameters were observed a fter placebo treatment. The level of UCP3 messenger ribonucleic acid (mRNA) increased S-fold (P < 0.005) in skeletal muscle and almost 2-fold (P < 0.0 5) in adipose tissue after GH treatment, with no changes observed after pla cebo treat-ment. Skeletal muscle UCP2 mRNA was slightly (25%), but signific antly (P < 0.05), decreased, whereas the level of UCP2 mRNA in adipose tiss ue was unaffected after GH treatment. The T-4 level was positively correlat ed with skeletal muscle UCP2 and UCP3 expression (r = 0.518; P < 0.05 and r = 0.463; P < 0.05, respectively). Furthermore, plasma free fatty acids wer e positively correlated with the expression of UCP2 (r = 0.573; P < 0.01) a nd UCP3 (r = 0.518; P < 0.05) in skeletal muscle. The marked increase in UC P3 expression after GH treatment indicates that the UCPs might play a role in the effects of GR on EE in GHD patients. Finally, the strong association between thyroid hormone and skeletal muscle UCP and the correlation betwee n plasma free fatty acids and UCP expression in skeletal muscle indicate th at these hormones/metabolites might influence UCP expression in humans as p reviously demonstrated in rodents.