Differentially Regulated Protein Kinase A (PKA) Activity in Adipose Tissue and Liver Is Associated With Resistance to Diet-Induced Obesity and Glucose Intolerance in Mice That Lack PKA Regulatory Subunit Type IIα

• DOI: 10.1210/en.2014-1122
• Publication Date: 2014-06-10T15:48:24Z
• Authors: Edra London; Maria Nesterova; Ninet Sinaii; Eva Szarek; Tatyana Chanturiya; Spyridon A. Mastr...; Oksana Gavrilova; Constantine A. St...
• Keywords: Steatosis; Knockout mouse

The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism all organ systems affected by obesity. PKA four regulatory (RIα, RIIα, RIβ, RIIβ) catalytic (Cα, Cβ, Cγ, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIβ, the primary adipose tissue or Cβ resulted lean phenotype resists diet-induced obesity associated metabolic complications. Here we report disruption ubiquitously RIIα mice (RIIαKO) confers resistance to obesity, glucose intolerance, hepatic steatosis. After 2-week high-fat diet exposure, RIIαKO weighed less than wild-type littermates. Over time this effect was more pronounced female were also leaner their counterparts, regardless diet. Decreased intake contributed attenuated weight gain mice. Additionally, deficiency caused differential regulation key organs: cAMP-stimulated activity decreased liver increased gonadal tissue. We conclude represents potential target for therapeutic interventions nonalcoholic fatty disease.