title: Regulation of uncoupling protein-2 and -3 by growth hormone in skeletal muscle and adipose tissue in growth hormone-deficient adults.
abstract: The newly described uncoupling proteins, UCP2 and UCP3, may play a role in regulating energy expenditure (EE) in humans. GH deficiency (GHD) is associated with decreased lean body mass, increased adiposity, and reduced EE, which are reversed by GH treatment. In the present study we investigated whether 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 = 11) treatment. GH treatment increased the amount of lean body mass by 4.5% (P < 0.05) and decreased body fat mass by 12% (P < 0.05), whereas no changes in these parameters were observed after placebo treatment. The level of UCP3 messenger ribonucleic acid (mRNA) increased 3-fold (P < 0.005) in skeletal muscle and almost 2-fold (P < 0.05) in adipose tissue after GH treatment, with no changes observed after placebo treatment. Skeletal muscle UCP2 mRNA was slightly (25%), but significantly (P < 0.05), decreased, whereas the level of UCP2 mRNA in adipose tissue was unaffected after GH treatment. The T4 level was positively correlated 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 were positively correlated with the expression of UCP2 (r = 0.573; P < 0.01) and UCP3 (r = 0.518; P < 0.05) in skeletal muscle. The marked increase in UCP3 expression after GH treatment indicates that the UCPs might play a role in the effects of GH on EE in GHD patients. Finally, the strong association between thyroid hormone and skeletal muscle UCP and the correlation between plasma free fatty acids and UCP expression in skeletal muscle indicate that these hormones/metabolites might influence UCP expression in humans as previously demonstrated in rodents.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus Amtssygehus, Denmark. amtssp@aau.dk
authors.forename: S B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: K
authors.initials: K
authors.lastname: Kristensen
authors.forename: S
authors.initials: S
authors.lastname: Fisker
authors.forename: J O
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: J S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: B
authors.initials: B
authors.lastname: Richelsen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001823:Body Composition / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics*; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
chemical_list: D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D019382:Human Growth Hormone