Systemic administration of epidermal growth factor increases UCP3 mRNA levels in skeletal muscle and adipose tissue in rats.
We have previously reported that systemic epidermal growth factor (EGF) treatment in rats reduces the amount of adipose tissue despite an unaltered food intake. The mitochondrial uncoupling proteins (UCP2 and UCP3) are thought to uncouple the respiratory chain and thus to increase energy expenditure. In order to find out whether the UCP system was involved in the EGF-induced weight loss, the effects of EGF on UCP2 and UCP3 in adipose tissue and skeletal muscle were investigated in the present study. Eight rats were treated with placebo or EGF (150 microg/kg/day) for seven days via mini-osmotic pumps. The EGF-treated rats gained significantly less body weight during the study period than the placebo-treated animals and had significantly less adipose tissue despite a similar food intake. The placebo group and the EGF group had similar UCP2 mRNA expression (in both adipose tissue and skeletal muscle), whereas the EGF-treated group compared to the placebo group had significantly higher UCP3 mRNA expression in both skeletal muscle (3.76 +/- 0.90 vs 8.41 +/- 0.87, P < 0.05) and in adipose tissue (6.38 +/- 0.71 vs 12.48 +/- 1.79, P < 0.05). In vitro studies with adipose tissue fragments indicated that the EGF effect probably is mediated indirectly as incubations with EGF (10 microM) were unable to affect adipose tissue UCP expression, whereas incubations with bromopalmitate stimulated both UCP2 and UCP3 mRNA expression twofold. Thus, EGF treatment in vivo was found to enhance UCP3 mRNA expression in both adipose tissue and skeletal muscle, which may indicate that the EGF effect on body composition might involve up-regulation of UCP3 in skeletal muscle and adipose tissue.
Pedersen
S B
SB
Department of Endocrinology and Internal Medicine, Aarhus Kommunehospital, Aarhus C, DK-8000, Denmark. AMTSSP@AAU.DK
Kristensen
K
K
Bruun
J M
JM
Flyvbjerg
A
A
Vinter-Jensen
L
L
Richelsen
B
B
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D005216:Fat Body / Q000187:drug effects; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604391:Ucp2 protein, rat; C000604394:Ucp3 protein, rat; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D004815:Epidermal Growth Factor