Overexpression of UCP-3 in skeletal muscle of mice results in increased expression of mitochondrial thioesterase mRNA.
Mice overexpressing human UCP-3 in skeletal muscle (UCP-3tg) are lean despite overeating, have increased metabolic rate, and their skeletal muscle mitochondria show increased proton conductance. The true function of UCP-3 however, has yet to be determined. It is assumed that UCP-3tg mice have increased fatty acid beta-oxidation to fuel their increased metabolic rate. In this study we have quantified skeletal muscle mRNA levels of a number of genes involved in fatty acid metabolism. mRNA levels of uncoupling protein-2, carnitine palmitoyl transferase-1beta and fatty acid binding proteins, and transporters were unchanged when compared to wild-type mice. Lipoprotein lipase mRNA was slightly, but significantly, increased by 50%. The most notable change in gene expression was a threefold increase in mitochondrial thioesterase (MTE-1) expression. In the face of a chronic increase in mitochondrial uncoupling these changes suggest that increased flux of fatty acids through the beta-oxidation pathway does not necessarily require marked changes in expression of genes involved in fatty acid metabolism. The large increase in MTE-1 both confirms the importance of this gene in situations where mitochondrial beta-oxidation is increased and supports the hypothesis that UCP-3 exports fatty acids generated by MTE-1 in the mitochondrion.
Moore
G B
GB
Department of Vascular Biology, GlaxoSmithKline, Harlow, Essex, United Kingdom.
Himms-Hagen
J
J
Harper
M E
ME
Clapham
J C
JC
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004247:DNA; D007473:Ion Channels; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D010170:Palmitoyl-CoA Hydrolase / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604392:UCP3 protein, human; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3; D004247:DNA; D010170:Palmitoyl-CoA Hydrolase