PKC and ERK mediate GH-stimulated lipolysis

Heather E. Bergan, Jeffrey D. Kittilson, Mark A. Sheridan

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

GH regulates several physiological processes in vertebrates, including the promotion of growth, an anabolic process, and the mobilization of stored lipids, a catabolic process. In this study, we used hepatocytes isolated from rainbow trout (Oncorhynchus mykiss) as a model to examine the mechanism of GH action on lipolysis. GH stimulated lipolysis as measured by increased glycerol release in both a time and a concentration-related manner. The promotion of lipolysis was accompanied by GH-stimulated phosphorylation of the lipolytic enzyme hormone-sensitive lipase (HSL). GH-stimulated lipolysis was also manifested by an increased expression of the two HSL-encoding mRNAs, HSL1 and HSL2. The signaling pathways that underlie GH-stimulated lipolysis were also studied. GH resulted in the activation of phospholipase C (PLC)/protein kinase C (PKC) and the MEK/ERK pathway, whereas JAK-STAT and the PI3K-Akt pathway were deactivated. The blockade of PLC/PKC and the MEK/ERK pathway inhibited GH-stimulated lipolysis and GH-stimulated phosphorylation of HSL as well as GH-stimulated HSL mRNA expression, whereas the blockade of JAK-STAT or the PI3K-Akt pathway had no effect on the activation of lipolysis or the expression of HSL stimulated by GH. These results indicate that GH promotes lipolysis by activating HSL and by enhancing the de novo expression of HSL mRNAs via the activation of PKC and ERK. These findings also suggest molecular mechanisms for activating the lipid catabolic actions of GH while simultaneously deactivating anabolic processes such as antilipolysis and the growth-promoting actions of GH.

Original languageEnglish
Pages (from-to)213-224
Number of pages12
JournalJournal of Molecular Endocrinology
Volume51
Issue number2
DOIs
StatePublished - 2013

Keywords

  • GH
  • Hormone-sensitive lipase
  • Lipids
  • Metabolism
  • Rainbow trout (oncorhynchus mykiss)
  • Signal transduction

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