Deletion of the RIIbeta-subunit of protein kinase A decreases body weight and increases energy expenditure in the obese, leptin-deficient ob/ob mouse.
Disruption of the RIIbeta regulatory subunit of protein kinase A (PKA) results in mice with a lean phenotype, nocturnal hyperactivity, and increased resting metabolic rate. In this report, we have examined whether deletion of RIIbeta would lead to increased metabolism and rescue the obese phenotype of the leptin-deficient ob/ob (ob) mouse. Body weight gain and food consumption were decreased, whereas basal oxygen consumption and nocturnal locomotor activity were increased in the double mutant animals compared with ob mice. The ob mice are unable to maintain body temperature when placed in a cold environment due to a loss of brown adipose tissue activation, and this cold sensitivity was partially rescued by concomitant disruption of RIIbeta. These findings indicate that PKA modifies the phenotype of the leptin-deficient mouse, leading to increases in both thermogenesis and energy expenditure.
Newhall
Kathryn J
KJ
Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.
Cummings
David E
DE
Nolan
Michael A
MA
McKnight
G Stanley
GS
D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001833:Body Temperature Regulation / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology*; D004734:Energy Metabolism; D017353:Gene Deletion; D015870:Gene Expression; D007473:Ion Channels; D020738:Leptin / Q000172:deficiency; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D024101:Mitochondrial Proteins; D009043:Motor Activity / Q000235:genetics; D009765:Obesity / Q000201:enzymology* / Q000235:genetics; D010101:Oxygen Consumption / Q000235:genetics; D012313:RNA / Q000378:metabolism; D000071256:Uncoupling Protein 1; D015854:Up-Regulation; D015431:Weight Loss
D002352:Carrier Proteins; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C517838:Prkar2b protein, mouse; D000071256:Uncoupling Protein 1; D012313:RNA; D017868:Cyclic AMP-Dependent Protein Kinases