Protein kinase A (PKA) RIIα knockout mice are resistant to diet-induced obesity

Friday, November 08, 2013 — Poster Session III
10:00 a.m. – 12:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NICHD	GEN-23

Authors

E London
O Gavrilova
M Nesterova
E Szarek
C A Stratakis

Abstract

The prevalence of obesity in the U.S. has reached a staggering 35.7% for adults and over 17% for children. It remains unclear why certain individuals are susceptible and others resist obesity in an “obesogenic environment”. The interaction between genes and diet is of particular interest. The Protein kinase A (PKA) signaling system is widely expressed in humans and mice, is a regulator of cellular metabolism, and is important in nearly all organ systems affected by obesity. Therefore, PKA is a good potential therapeutic target for obesity. PKA has four regulatory (RIα, RIIα, RIβ, RIIβ) and four catalytic subunit isoforms (Cα, Cβ, C, Prkx). While not well understood, knockout (KO) of RIIβ, highly expressed in brain, brown and white adipose tissue, results in a genetically lean mouse. Unlike the more tissue-specific expression of RIIβ, RIIα is expressed ubiquitously. We found that RIIα deficiency confers resistance to diet-induced obesity (DIO), glucose intolerance, and fatty liver in mice chronically fed HFD. PKA activity increased in adipose and decreased in liver. After 2wk HFD, RIIα KO mice weighed less than WT littermates, an effect that was more pronounced in females over time. PKA RIIα represents a new potential target for therapeutic interventions in obesity.