Session: SAT 708-722-Obesity: Response to Interventions
Poster Board SAT-712
Edra London, PhD; and Constantine A. Stratakis, MD, DMedSci
Section on Endocrinology and Genetics, Program on Developmental Endocrinology & Genetics (PDEGEN) Eunice Kennedy ShriverNational Institute of Child Health & Human Development (NICHD), National Institutes of Health, Bethesda, MD
Cyclic AMP is an essential second messenger that regulates cellular metabolism as well as proliferation, secretion, and differentiation. Protein kinase A (PKA) mediates the effects of cAMP via signals originating from G-protein coupled receptors (GPCRs) that are activated by a vast number of hormones, neurotransmitters and other small molecules and proteins. PKA has four regulatory subunit isoforms (RIα, RIIα, RIβ, RIIβ) and four catalytic subunit isoforms (Cα, Cβ, Cγ, Prkx). Adipocytes and hepatocytes are two important cells in which control of glucose and lipid metabolism is mediated via GPCRs through the cAMP signal transduction pathway. Additionally, adipose tissue (AT) and liver are recognized as key organs in the peripheral regulation of energy homeostasis. We hypothesized that diet-induced obese (DIO) mice would display dysregulation of the PKA system in liver and AT that may favor and help to maintain obesity. Obesity was induced in C57BL/6 mice by providing them with ad libitum access to high-fat diet (HFD) for 14 weeks. Age and sex-matched controls were given ad libitum access to standard (low fat) chow for the same time period. As expected, DIO mice had impaired glucose tolerance, increased adiposity, and developed fatty livers. DIO female mice had significantly decreased mRNA expression of PKA regulatory subunits RIα, RIIα and catalytic subunits Cα and Cβ. In gonadal AT, PKA subunits RIα and Cβ mRNA levels in DIO female mice were significantly lower than those of lean controls. Trends of decreased PKA subunit mRNA were also observed in DIO males when compared to their lean counterparts. Initial protein expression analyses indicate a decrease in expression of PKA subunits in DIO mice in liver and AT. Current experiments focus on the question of whether changes in PKA occur as a result of increased adiposity and/or impaired glucose tolerance or whether diet can initiate these changes acutely. Shorter-term HFD feeding that includes earlier time points that precede the onset of obesity and additional time points during the early development of obesity will provide insight into this previously undescribed phenomenon. We conclude that PKA activity is suppressed in liver and AT of wild type mice that became obese after chronic HFD intake.
Nothing to Disclose: EL, CAS
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