Abstract 12109: Depot-Specific Abnormalities in Adipose Tissue Insulin Signaling in a Porcine Model of Metabolic Syndrome
Background: The clinical metabolic syndrome (Met Syn) is associated with systemic insulin resistance and with increased mass and dysfunction of subcutaneous (SAT) and visceral adipose tissue. Accumulation and dysfunction of epicardial adipose tissue (EAT) have been associated with cardiovascular risk in Met Syn. We previously characterized a porcine dietary model of Met Syn that demonstrates defective insulin signaling in cardiac and skeletal muscle and arterial wall, and impaired cardiac tolerance to ischemia. We used this model in this study to assess effects of MetSyn on insulin signaling in SAT and EAT.
Methods: Yucatan micropigs (n=16) were fed a diet enriched in saturated fat (coconut oil) and high fructose corn syrup for 6 months to induce obesity and MetSyn. Yucatan micropigs or domestic farm pigs fed standard low-fat chow served as lean controls (n=23). In each pig, SAT and EAT were sampled in the absence of exogenous insulin stimulation and/or 10 min after a saturating dose of insulin (10 U/kg, IV). Phosphatidylinositol 3-kinase (PI3K) activity was measured by thin layer chromatography. Phosphorylation of Akt (pAkt) was assessed by Western blotting.
Results: In controls, insulin significantly stimulated PI3K activity, pAkt, and IRS-1 association of the p85 and p110 subunits of PI3K, in both SAT and EAT. MetSyn pigs developed obesity, elevated blood pressure, dyslipidemia, and systemic insulin resistance (by IV glucose tolerance testing). In contrast to controls, insulin stimulation in Met Syn pigs produced no activation of PI3K in either SAT or EAT, no increase in pAkt in SAT, only borderline increase in pAkt in EAT (p=0.05), and no significant IRS-1 association of p85α or p110 in either fat depot. In contrast to prior findings in this model in cardiac muscle and arterial wall, neither total p85α nor phosphorylation of IRS-1 at Ser307 differed between Met Syn and control pigs in either SAT or EAT.
Conclusions: In a porcine model of Met Syn, insulin signaling through PI3K and Akt is defective in both SAT and EAT, mirroring findings in cardiac and skeletal muscle and arterial wall. However, unlike these other tissues, abnormal insulin signaling in fat of MetSyn pigs is not attributable to increased expression of p85α or to Ser307 phosphorylation of IRS-1.
Author Disclosures: G.G. Schwartz: None. J.W. Leitner: None. L. Lu: None. S. Ye: None. A. Pendyal: None. R. Pereira: None. C.C. Wang: None. J.E. Reusch: None. C.R. Greyson: None.
- © 2014 by American Heart Association, Inc.