Effects of obesity and stable weight reduction on UCP2 and UCP3 gene expression in humans.
OBJECTIVE
The molecular determinants of energy expenditure are presently unknown. Recently, two uncoupling protein homologues, UCP2 and UCP3, have been identified. UCP2 is expressed widely, and UCP3 is expressed abundantly in skeletal muscle. Both could be important regulators of energy balance. In this paper, we investigated whether altered UCP2 and UCP3 mRNA levels are associated with obesity or weight reduction.


METHODS
UCP2, UCP3 long and short mRNA levels were examined in skeletal muscle and in white adipose tissue of lean, obese, and weight-reduced individuals by RNase protection assay.


RESULTS
Expression of UCP2, UCP3S, and UCP3L mRNA in skeletal muscle was similar in lean individuals and in individuals with obesity at stable weight. In contrast, UCP3L and UCP3S mRNAs were decreased by 38% (p<0.0059) and 48% (p<0.0047), respectively, in 20% weight-reduced patients with obesity at stable weight. In contrast, UCP2 mRNA levels were increased by 30% in skeletal muscle of 20% weight-reduced subjects with obesity. In a different set of patients, mostly lean, UCP3L mRNA in skeletal muscle was decreased by 28% (p = 0.0425) after 10% weight reduction at stable weight. Expression of UCP2 mRNA in subcutaneous adipose tissue was similar in lean individuals and in individuals with obesity, and was increased by 58% during active weight loss.


CONCLUSIONS
Stabilization at reduced body weight in humans is associated with a decrease in UCP3 mRNA in muscle. It is possible that reduced UCP3 expression could contribute to decreased energy expenditure in weight-stable, weight-reduced individuals.
Vidal-Puig
A
A
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Rosenbaum
M
M
Considine
R C
RC
Leibel
R L
RL
Dohm
G L
GL
Lowell
B B
BB
D000273:Adipose Tissue / Q000737:chemistry; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008928:Mitochondria / Q000737:chemistry; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000737:chemistry; D009765:Obesity / Q000235:genetics* / Q000628:therapy*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D015431:Weight Loss
D002352:Carrier Proteins; 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