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|Title:||Exchange protein directly activated by cAMP 1 plays an important role in β3-adrenergic induction of UCP1 in WAT and thermogenesis via regulating lipolysis|
|Authors:||Chen, Y;Tai, ACP;Kai, AKL;Tam, S;Lam, KSL;Chung, SSM;Xu, A;Chung, SK|
|Publisher:||American Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/|
|Description:||Late Breaking Abstracts: Session - Integrated Physiology/Obesity: no. 185-LB|
Open Access Journal
Pharmaceutical 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.
|Standard no:||The 73rd Scientific Sessions of the American Diabetes Association (ADA), Chicago, IL., 21-25 June 2013. In Diabetes, 2013, v. 62 suppl. 1A, p. LB48, abstract no. 185-LB|
|Appears in Collections:||Department of Anatomy|
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