| First Author | London E | Year | 2014 |
| Journal | Endocrinology | Volume | 155 |
| Issue | 9 | Pages | 3397-408 |
| PubMed ID | 24914943 | Mgi Jnum | J:217015 |
| Mgi Id | MGI:5612921 | Doi | 10.1210/en.2014-1122 |
| Citation | London E, et al. (2014) 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 IIalpha. Endocrinology 155(9):3397-408 |
| abstractText | The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism in all organ systems affected by obesity. PKA has four regulatory (RIalpha, RIIalpha, RIbeta, RIIbeta) and four catalytic (Calpha, Cbeta, Cgamma, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIbeta, the primary PKA regulatory subunit in adipose tissue or knockout of the catalytic subunit Cbeta resulted in a lean phenotype that resists diet-induced obesity and associated metabolic complications. Here we report that the disruption of the ubiquitously expressed PKA RIIalpha subunit in mice (RIIalphaKO) confers resistance to diet-induced obesity, glucose intolerance, and hepatic steatosis. After 2-week high-fat diet exposure, RIIalphaKO mice weighed less than wild-type littermates. Over time this effect was more pronounced in female mice that were also leaner than their wild-type counterparts, regardless of the diet. Decreased intake of a high-fat diet contributed to the attenuated weight gain in RIIalphaKO mice. Additionally, RIIalpha deficiency caused differential regulation of PKA in key metabolic organs: cAMP-stimulated PKA activity was decreased in liver and increased in gonadal adipose tissue. We conclude that RIIalpha represents a potential target for therapeutic interventions in obesity, glucose intolerance, and nonalcoholic fatty liver disease. |
