Regulation of uncoupling protein (UCP) 2 and 3 in adipose and muscle tissue by fasting and growth hormone treatment in obese humans.
OBJECTIVE
To investigate whether the expression of uncoupling proteins (UCP2 and UCP3) was affected by a very low calorie diet (VLCD) and growth hormone (GH) treatment for 4 weeks.


METHODS
A randomized, placebo-controlled intervention study of VLCD with or without concomitant GH-treatment.


METHODS
Seventeen obese women (body mass index, BMI=42.1+/-1.4 kg/m2 (range 31.8-54.5 kg/m2)) treated with VLCD for 4 weeks and randomized to concomitant placebo treatment (n=9) or GH treatment (n=8).


METHODS
Fat mass and lean body mass were measured by dual-energy X-ray absorptiometry. Energy expenditure (EE) was measured by indirect calorimetry. UCP2 and UCP3 mRNA were measured in adipose tissue and skeletal muscle biopsies before VLCD and after VLCD+/-GH-treatment by reverse transcription polymerase chain reaction (RT-PCR).


RESULTS
VLCD treatment resulted in a mean weight loss of 5.23 kg+/-0.8 (P<0.01), a 4.1% decrease in EE (P<0.05) and a 24% decrease in UCP3 mRNA in adipose tissue (P<0.03), whereas adipose tissue UCP2 mRNA and skeletal muscle UCP2 and UCP3 mRNA levels were unchanged. GH-treatment had no effects on EE, changes in body weight or UCP mRNA level. In multiple regression analysis the change in EE caused by VLCD was significantly correlated with changes in adipose tissue UCP2 mRNA (r=0.66, P<0.02) and a tendency towards a significant association with the change in adipose tissue UCP3 mRNA (r=0.45, P=0.09), but not with change in body weight, skeletal muscle UCP2 or UCP3 mRNA levels.


CONCLUSIONS
VLCD for 4 weeks decreased UCP3 mRNA expression in human adipose tissue, whereas GH-treatment had no effect on UCP expression. Multiple regression analysis demonstrated that changes in adipose tissue UCP2 and probably UCP3 mRNA were correlated with the change in EE. These findings indicate that UCPs in adipose tissue in very obese individuals might play a role for the reduction in EE observed during energy restriction.
Pedersen
S B
SB
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus Amtssygehus, DK-8000 Aarhus C, Denmark. amtssp@aau.dk
Borglum
J D
JD
Kristensen
K
K
Norrelund
H
H
Otto
J
J
Jorgensen
L
L
Richelsen
B
B
D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D001823:Body Composition / Q000187:drug effects; D002153:Calorimetry, Indirect; D002352:Carrier Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D004038:Diet, Reducing; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007279:Injections, Subcutaneous; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism*; D011506:Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D017931:DNA Primers; 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; D013006:Growth Hormone