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This Article Accepted manuscript (PDF) All Versions of this Article: JME-08-0130v1 42/1/57    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, T. Articles by Xu, G. Search for Related Content PubMed PubMed Citation Articles by Zhang, T. Articles by Xu, G.

T Zhang, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
J He, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
C Xu, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
L Zu, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
H Jiang, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
S Pu, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
X Guo, Department of Endocrinology, the First Hospital of Peking University, Beijing, China
G Xu, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100083, China

Correspondence: Guoheng Xu, Email: xug{at}bjmu.edu.cn

Abstract

The mobilization of free fatty acids (FFA) from adipose tissue to the bloodstream primarily depends on triacylglycerol lipolysis in adipocytes. Catecholamines are major hormones that govern lipolysis through elevating cellular cAMP production and activating protein kinase A (PKA) and extracellular signal-related kinase 1/2 (ERK1/2). Obesity and type 2 diabetes are associated with elevated level of systemic FFA, which restricts glucose utilization and induces insulin resistance. The biguanide metformin exerts its antihyperglycemic effect by enhancing insulin sensitivity, which is associated with decreased levels of circulating FFA. In this study, we examined the characteristics and basis of the inhibitory effect of metformin on adrenergic-stimulated lipolysis in primary rat adipocytes. We measured the release of FFA and glycerol as an index of lipolysis and examined the major signalings of the lipolytic cascade in primary rat adipocytes. Metformin at 250~500 µM efficiently attenuated FFA and glycerol release from the adipocytes stimulated with 1 µM isoproterenol. To elucidate the basis for this antilipolytic action, we showed that metformin decreased cellular cAMP production, reduced the activities of PKA and ERK, and attenuated the phosphorylation of perilipin during isoproterenol-stimulated lipolysis. Further, metformin suppressed isoproterenol-promoted lipase activity but did not affect the translocation of hormone-sensitive lipase from the cytosol to lipid droplets in adipocytes. This study provides evidence that metformin acts on adipocytes to suppress the lipolysis response to catecholamine. This antilipolytic effect could be a cellular basis for metformin decreasing plasma FFA levels and improving insulin sensitivity.

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				C. Xu, J. He, H. Jiang, L. Zu, W. Zhai, S. Pu, and G. Xu Direct Effect of Glucocorticoids on Lipolysis in Adipocytes Mol. Endocrinol., August 1, 2009; 23(8): 1161 - 1170. [Abstract] [Full Text] [PDF]