Genetically lean mice result from targeted disruption of the RIIβ subunit of protein kinase A
Copyright policy )Genetically lean mice result from targeted disruption of the RIIβ subunit of protein kinase A
Cyclic AMP is an important second messenger in the coordinated regulation of cellular metabolism. Its effects are mediated by cAMP-dependent protein kinase (PKA), which is assembled from two regulatory (R) and two catalytic (C) subunits. In mice there are four R genes (encoding RI alpha, RI beta, RII alpha, and RII beta) and two C gene (encoding C alpha and C beta), expressed in tissue-specific patterns. The RII beta isoform is abundant in brown and white adipose tissue and brain, with limited expression elsewhere. To elucidate its functions, we generated RII beta knockout mice. Here we report that mutants appear healthy but have markedly diminished white adipose tissue despite normal food intake. They are protected against developing diet-induced obesity and fatty livers. Mutant brown adipose tissue exhibits a compensatory increase in RI alpha, which almost entirely replaces lost RII beta, generating an isoform switch. The holoenzyme from mutant adipose tissue binds cAMP more avidly and is more easily activated than wild-type enzyme. This causes induction of uncoupling protein and elevations of metabolic rate and body temperature, contributing to the lean phenotype. Our results demonstrate a role for the RII beta holoenzyme in regulating energy balance and adiposity.
- University of Washington United States
- University of Mary United States
Leptin, Male, Mice, Knockout, Body Weight, Membrane Proteins, Cyclic AMP-Dependent Protein Kinases, Dietary Fats, Ion Channels, Isoenzymes, Mitochondrial Proteins, Eating, Mice, Adipose Tissue, Adipose Tissue, Brown, Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit, Cyclic AMP, Animals, Female, Carrier Proteins, Energy Metabolism
Leptin, Male, Mice, Knockout, Body Weight, Membrane Proteins, Cyclic AMP-Dependent Protein Kinases, Dietary Fats, Ion Channels, Isoenzymes, Mitochondrial Proteins, Eating, Mice, Adipose Tissue, Adipose Tissue, Brown, Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit, Cyclic AMP, Animals, Female, Carrier Proteins, Energy Metabolism
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).395 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!