The role of uncoupling protein 1 in the metabolism and adiposity of RII beta-protein kinase A-deficient mice.
Mice lacking the RII beta regulatory subunit of protein kinase A exhibit a 50% reduction in white adipose tissue stores compared with wild-type littermates and are resistant to diet-induced obesity. RII beta(-/-) mice also have an increase in resting oxygen consumption along with a 4-fold increase in the brown adipose-specific mitochondrial uncoupling protein 1 (UCP1). In this study, we examined the basis for UCP1 induction and tested the hypothesis that the induced levels of UCP1 in RII beta null mice are essential for the lean phenotype. The induction of UCP1 occurred at the protein but not the mRNA level and correlated with an increase in mitochondria in brown adipose tissue. Mice lacking both RII beta and UCP1 (RII beta(-/-)/Ucp1(-/-)) were created, and the key parameters of metabolism and body composition were studied. We discovered that RII beta(-/-) mice exhibit nocturnal hyperactivity in addition to the increased oxygen consumption at rest. Disruption of UCP1 in RII beta(-/-) mice reduced basal oxygen consumption but did not prevent the nocturnal hyperactivity. The double knockout animals also retained the lean phenotype of the RII beta null mice, demonstrating that induction of UCP1 and increased resting oxygen consumption is not the cause of leanness in the RII beta mutant mice.
Nolan
Michael A
MA
Department of Pharmacology, Box 357750, University of Washington, Seattle, Washington 98195-7750, USA.
Sikorski
Maria A
MA
McKnight
G Stanley
GS
D000273:Adipose Tissue / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D005786:Gene Expression Regulation; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D009765:Obesity / Q000209:etiology*; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013696:Temperature; D013851:Thinness / Q000209:etiology* / Q000235:genetics; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C517838:Prkar2b protein, mouse; D012333:RNA, Messenger; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D017868:Cyclic AMP-Dependent Protein Kinases