Effects of fasting on muscle mitochondrial energetics and fatty acid metabolism in Ucp3(-/-) and wild-type mice.
Uncoupling protein-3 (UCP3) is a mitochondrial carrier protein of as yet undefined physiological function. To elucidate characteristics of its function, we studied the effects of fasting on resting metabolic rate, respiratory quotient, muscle Ucp3 expression, and mitochondrial proton leak in wild-type and Ucp3(-/-) mice. Also analyzed were the fatty acid compositions of skeletal muscle mitochondria in fed and fasted Ucp3(-/-) and wild-type mice. In wild-type mice, fasting caused significant increases in Ucp3 (4-fold) and Ucp2 (2-fold) mRNA but did not significantly affect mitochondrial proton leak. State 4 oxygen consumption was not affected by fasting in either of the two groups. However, protonmotive force was consistently higher in mitochondria of Ucp3(-/-) animals (P = 0.03), and fasting further augmented protonmotive force in Ucp3(-/-) mice; there was no effect in wild-type mitochondria. Resting metabolic rates decreased with fasting in both groups. Ucp3(-/-) mice had higher respiratory quotients than wild-type mice in fed resting states, indicating impaired fatty acid oxidation. Altogether, results show that the fasting-induced increases in Ucp2 and Ucp3 do not correlate with increased mitochondrial proton leak but support a role for UCP3 in fatty acid metabolism.
Bézaire
V
V
Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Hofmann
W
W
Kramer
J K
JK
Kozak
L P
LP
Harper
M E
ME
D000818:Animals; D016718:Arachidonic Acid / Q000032:analysis; D001481:Basal Metabolism; D001835:Body Weight; D002153:Calorimetry, Indirect; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D004281:Docosahexaenoic Acids / Q000032:analysis; D004734:Energy Metabolism; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism*; D005502:Food; D007473:Ion Channels; D007700:Kinetics; D019787:Linoleic Acid / Q000032:analysis; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000737:chemistry / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D009929:Organ Size; D010101:Oxygen Consumption; D019308:Palmitic Acid / Q000032:analysis; D011506:Proteins / Q000032:analysis; D011522:Protons; D012333:RNA, Messenger / Q000032:analysis; D013229:Stearic Acids / Q000032:analysis; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D011522:Protons; D012333:RNA, Messenger; D013229:Stearic Acids; C000604390:Ucp2 protein, mouse; C000604393:Ucp3 protein, mouse; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019308:Palmitic Acid; C031183:stearic acid; D019787:Linoleic Acid