Uncoupling protein-3 gene expression: reduced skeletal muscle mRNA in obese humans during pronounced weight loss.
OBJECTIVE
Uncoupling protein-3 is a member of a protein family that serves to dissipate energy in the form of heat thereby modulating energy expenditure. Alternative processing of uncoupling protein-3 transcripts results in two mRNA species that encode a large and small protein, perhaps differing in functional activity. Since obesity is associated with disrupted energy homeostasis, we measured muscle mRNA expression in morbidly obese and lean subjects.


METHODS
The two uncoupling protein-3 mRNA species were quantified in muscle tissue using an RNase protection assay. Gene locus effects on mRNA expression were studied by quantitative allele-specific primer extension.


RESULTS
In both obese and lean subjects, the mRNA species encoding the small protein isoform was twice as abundant as the mRNA species encoding the large protein isoform. Neither the total uncoupling protein-3 mRNA expression nor the molar abundance ratios of the two mRNA species differed between obese and lean male or female subjects. Women who had lost 37+/-22 kg of weight in response to dietary restriction and continued a hypocaloric diet displayed lower mRNA than obese (p<0.005) or lean women (p<0.05). Primer extension assays in lean and obese subjects showed similar allelic mRNA abundance in all but one subject studied.


CONCLUSIONS
Muscle expression of the two uncoupling protein-3 mRNA species is similar in obese and lean people. In obese patients, prolonged hypocaloric diet downregulates uncoupling protein-3 mRNA expression in muscle and can thereby enhance its energy efficiency. Sequence substitutions at the gene locus may only be minor determinants of mRNA expression in muscle tissue.
Esterbauer
H
H
Department of Laboratory Medicine, Landeskrankenanstalten Salzburg, Austria.
Oberkofler
H
H
Dallinger
G
G
Breban
D
D
Hell
E
E
Krempler
F
F
Patsch
W
W
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D009767:Obesity, Morbid / Q000235:genetics* / Q000503:physiopathology* / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D014158:Transcription, Genetic; D000071247:Uncoupling Protein 3; D015431:Weight Loss
D002352:Carrier Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3