Exchange protein directly activated by cAMP 1 plays an important role in β3-adrenergic induction of UCP1 in WAT and thermogenesis via regulating lipolysis

Open Access JournalLate Breaking Abstracts: Session - Integrated Physiology/Obesity: no. 185-LBPharmaceutical enhancement of uncoupling protein1 (UCP1) and thermogenesis has drawn great interest to counteract obesity. Previously, the exchange protein directly activated by cAMP 1 (Epac1)-deficient mice showed less induction of beige cells with a significantly less UCP1 expression in white adipose tissue (WAT) and lower circulating free fatty acid (FFA) after chronic CL316,243 (a β3-adrenergic receptor agonist, CL, 1mg/kg/day for 10 days) administration, compared to that of wild type (wt) mice. To further study the role of Epac1 in β3-adrenergic induction of UCP1 and its function, energy expenditure and thermogenesis were determined. By indirect calorimetry, the Epac1-deficient mice showed slightly lower oxygen consumption from 9-16 hours after CL (1mg/kg) administration compared to that of wt mice. By using rectal thermometer, continuously lower rectal temperature within 30 min after the ninth dose of CL administration was observed in the Epac1-deficient mice relative to that of wt mice. These results suggest that in the absence of Epac1, increase of energy expenditure and thermogenesis induced by β3-adrenergic activation are compromised, which could be due to lower FFA and UCP1 induced by CL in the Epac1-deficent mice. To test whether the reduced FFA is due to compromised lipolysis, glycerol release from WAT explants was examined ex vivo. Interestingly, Epac1-deficient WAT explants showed impaired CL-stimulated glycerol release, indicating that absence of Epac1 diminishes β3-adrenergic receptor mediated lipolysis in WAT. In addition, Western blot showed that phosphorylation of hormone sensitive lipase at Ser660 by protein kinase A (PKA) was not different in Epac1-deficient WAT explants incubated with CL (10uM) for 10 min, compared to that of wt mice. Taken together, Epac1 plays an important role in β3-adrenergic induction of UCP1 in WAT and thermogenesis via mediating lipolysis independent of PKA.link_to_OA_fulltex

Exchange protein directly activated by cAMP 1 is involved in β3-adrenergic induction of brown adipose tissue in white adipose tissue

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Exchange protein directly activated by cAMP 1 is involved in β3-adreneric induction of brown adipose tissue in white adipose tissue

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