Role of AMP-activated Protein Kinase in Cyclic AMP-dependent Lipolysis In 3T3-L1 Adipocytes

Wu Yin, James Mu, Morris J. Birnbaum
2003 Journal of Biological Chemistry  
AMP-activated protein kinase (AMPK) is a phylogenetically conserved intracellular energy sensor that has been implicated as a major regulator of glucose and lipid metabolism in mammals. However, its possible role in mediating or influencing the adrenergic control of lipolysis in adipocytes remains uncertain. In this study, we utilized the murine cultured preadipocyte line 3T3-L1 to examine this question. Treatment of adipocytes with isoproterenol or forskolin promoted the phosphorylation of
more » ... at a critical activating Thr-172 residue in a dose-and time-dependent manner. This correlated well with a stimulation of the activity of AMPK, as measured in the immune complex. Analogs of cAMP mimicked the effect of isoproterenol and forskolin on AMPK phosphorylation. Treatment of adipocytes with insulin reduced both basal and forskolin-induced AMPK phosphorylation via a pathway dependent on phosphatidylinositol 3-kinase. Overexpression of a dominant-inhibitory mutant of AMPK blocked isoproterenolinduced lipolysis by ϳ50%. These data indicate that there exists a novel pathway by which cAMP can lead to the activation of AMPK, and in adipocytes, this is required for maximal activation of lipolysis.
doi:10.1074/jbc.m308484200 pmid:12941946 fatcat:57ivxrgq6fdxzcto5fhwuypzay