Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Analyzing PKA signaling in adipose depots (#226)

Barton Wicksteed 1 , Lorna M Dickson 1 , Johanne H Ellenbroek 1 , Ronald N Cohen 1
  1. University of Chicago, Chicago, IL, United States

Lipid deposition in adipose tissue is likely to benefit metabolic health, by preventing ectopic lipid deposition in other metabolically important tissues, including liver and skeletal muscle. Moreover, lipid storage in subcutaneous adipose is considered more metabolically healthy than storage in visceral depots, including mesenteric and epididymal adipose. Adipose lipolysis is regulated by cyclic AMP (cAMP), through the activation of the cAMP-dependent protein kinase, PKA, which phosphorylates target proteins, including perilipin and hormone sensitive lipase. We hypothesized that the activation of PKA in adipose should promote lipolysis and impair metabolic health. Heterozygous PKA-CαR mice, which carry a Cre-inducible activating mutation in the PKA alpha catalytic subunit, were crossed to heterozygous adiponectin-Cre mice. One quarter of offspring were PKA-CαR+ and Cre+, hereafter named APN-caPKA mice, and the other genotype offspring (wildtype, Cre+ and PKA-CαR+) were used as littermate controls. Upon weaning of male mice onto a 60% high fat diet (HFD) at 4 weeks of age, APN-caPKA mice were significantly lighter than littermates. By 24-26 weeks of age APN-caPKA were significantly lighter than littermates, had less adipose tissue (by DEXA), had lighter epididymal fat padsand were also more glucose tolerant. These data indicate that activating adipose PKA does drive lipolysis, but that this is not detrimental for metabolic health. Metabolic cage studies are currently being conducted to determine whether an increased metabolic rate may explain this finding. It has been previously shown that activation of PKA in brown adipose tissue, where adiponectin is also expressed, promotes increased energy expenditure. Comparative analyses of the expression profile of PKA subunits between adipose depots indicate suppression of PKA activity in subcutaneous adipose, consistent with it being a more stable site of lipid storage.