Xenical Research Today is a free monthly online journal that collates and summarizes the latest research about Xenical, including details on orlistat, side-effects, obesity, weight loss, dieting. | ||||||||
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AMP-activated protein kinase (AMPK) is activated as a consequence of lipolysis in the adipocyte: potential mechanism and physiological relevance.Gauthier MS, Miyoshi H, Souza SC, Cacicedo JM, Saha AK, Greenberg AS, Ruderman NB Medicine, Diabetes and Metabolism Research Unit, Boston University School of Medicine, Boston, MA 02118. AMPK is activated in adipocytes during exercise and other states in which lipolysis is stimulated. However, the mechanism(s) responsible for this effect and its physiological relevance are unclear. To examine these questions, 3T3-L1 adipocytes were treated with agents that increase cAMP levels (isoproterenol, forskolin, isobutylmethylxanthine) which are known to stimulate lipolysis and activate AMPK. When lipolysis was partially inhibited by co-incubating the cells with the general lipase inhibitor orlistat, AMPK activation by these agents was also partially diminished, but the increases in cAMP levels and PKA activity were unaffected. Likewise, shRNA-mediated silencing of adipose tissue triglyceride lipase inhibited both forskolin-stimulated lipolysis and AMPK activation but not that of PKA. Forskolin treatment increased the AMP:ATP ratio (4-fold), and this too was reduced by orlistat. When acyl-CoA synthetase, which catalyzes the conversion of fatty-acids to fatty-acyl-CoA, was inhibited with triacsin C, both the increases in AMPK activity and in AMP:ATP ratio were blunted. Isoproterenol-stimulated lipolysis was accompanied by an increase in reactive oxygen species production, an effect that was quintupled in adipocytes incubated with the AMPK inhibitor compound C. The isoproterenol-induced increase in the AMP:ATP ratio was also much greater in these cells, indicating they were more energy stressed. In conclusion, the results indicate that activation of AMPK in adipocytes by agents that increase cAMP levels is a consequence of lipolysis and not the direct result of increases in cAMP levels or PKA activity. They also suggest that AMPK activation in this setting is caused by an increase in the AMP:ATP ratio that appears to be due, at least in part, to the acylation of fatty-acids. Finally, this AMPK activation appears to restrain the energy depletion and oxidative stress caused by lipolysis. Published 8 April 2008 in J Biol Chem.
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