Diabetes, Metabolic Syndrome and Obesity (Sep 2019)

Effects of liraglutide on lipolysis and the AC3/PKA/HSL pathway

  • Li Z,
  • Yang P,
  • Liang Y,
  • Xia N,
  • Li Y,
  • Su H,
  • Pan H

Journal volume & issue
Vol. Volume 12
pp. 1697 – 1703

Abstract

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Zhengming Li1,*, Pijian Yang2,*, Yuzhen Liang1,*, Ning Xia2,*, Yingrong Li1, Hongye Su1, Hailin Pan1 1Department of Endocrinology and Metabolism, Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuzhen LiangDepartment of Endocrinology and Metabolism, Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, People’s Republic of ChinaEmail [email protected] XiaDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, People’s Republic of ChinaEmail [email protected]: Liraglutide reduces blood glucose, body weight and blood lipid levels. Hormone-sensitive lipase (HSL) is a key enzyme in lipolysis. Evidence from our and other studies have demonstrated that adenylate cyclase 3 (AC3) is associated with obesity and can be upregulated by liraglutide in obese mice. In the present study, we investigated whether hepatic HSL activity is regulated by liraglutide and characterized the effect of liraglutide in the AC3/protein kinase A (PKA)/HSL signalling pathway.Methods: Obese mice or their lean littermates were treated with liraglutide or saline for 8 weeks. Serum was collected for the measurement of insulin and lipids. We investigated hepatic AC3, HSL and phosphorylated HSL Ser-660 (p-HSL(S660)) protein expression levels andAC3 and HSL mRNA expression levels and cyclic adenosine monophosphate (cAMP), PKA activity in liver tissue.Results: Liraglutide treatment decreased triglycerides (TGs) and free fatty acids (FFAs), increased glycerol, and upregulated hepatic AC3 and p-HSL(s660) levels and cAMP and PKA activities.Conclusion: The results suggest that liraglutide can upregulates AC3/PKA/HSL pathway and may promotes lipolysis.Keywords: liraglutide, obesity, lipolysis, adenylate cyclase 3, hormone-sensitive lipase

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