Activation of AMP Kinase by Adiponectin and Insulin

Adiponectin activates AMP-activated protein kinase (AMPK) in adipocytes but the underlying mechanism remained unclear. Qingqing Liu tested the hypothesis that AMP, generated in activating fatty acids to their CoA derivatives in a reaction catalyzed by acyl-CoA synthetases, is involved in AMPK activation by adiponectin. Moreover, in adipocytes insulin affects the subcellular localization of the acyl-CoA synthetase FATP1. Thus she also tested if insulin activates AMPK in adipocytes, and if so through a similar mechanism. Qingqing examined these hypotheses by measuring the AMP/ATP ratio and AMPK activation upon adiponectin and insulin stimulation, and after knocking down acyl-CoA synthetases in adipocytes. She showed that adiponectin activation of AMPK is accompanied by a ~ 2-fold increase in the cellular AMP/ATP ratio. Moreover, FATP1 and Acsl1, the two major acyl-CoA synthetase isoforms in adipocytes, are essential for AMPK activation by adiponectin. Qingqing also showed that after 40 min. insulin activated AMPK in adipocytes, which was coupled with a 5-fold increase in the cellular AMP/ATP ratio. Knockdown studies show that FATP1 and Acsl1 are required for these processes, as well as for stimulation of long chain fatty acid uptake by adiponectin and insulin. These studies demonstrate that a change in cellular energy state is associated with AMPK activation by both adiponectin and insulin, which requires the activity of FATP1 and Acsl1.