Contractions induce phosphorylation of the AMPK site Ser 565 in hormone-sensitive lipase in muscle

Abstract

Intramyocellular triglyceride is an important energy store which is related to insulin resistance. Mobilization of fatty acids from this pool is probably regulated by hormone-sensitive lipase (HSL), which has recently been shown to exist in muscle and to be activated by epinephrine via PKA and by contractions via PKC and ERK. 5 ′ AMP-activated protein kinase (AMPK) is an intracellular fuel gauge which regulates metabolism. In this study we incubated rat soleus muscle to investigate if AMPK influences HSL during 5 min of repeated tetanic contractions. An eightfold increase in AMPK activity was accompanied by a 2.5-fold increase in phosphorylation of the AMPK-site Ser 565 in HSL ( p<0.05). Inhibition of PKC by Calphostin C abolished the contraction-mediated HSL activation while HSL-Ser 565 phosphorylation was not reduced. The study indicates that during contractions AMPK phosphorylates HSL in Ser 565, but this phosphorylation is not directly responsible for the contraction-induced activation of HSL.