Gene Expression in Skeletal Muscle after an Acute Intravenous GH Bolus in Human Subjects: Identification of a Mechanism Regulating ANGPTL4

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Growth hormone (GH) acutely stimulates lipolysis and fat oxidation, a process which operates postabsorptively and involves activation of the JAK-STAT pathway in the target tissue; no in vivo data exist regarding subsequent GH-regulated gene transcription. We obtained serum samples and muscle biopsies in human subjects before and 2 h after administration of a GH bolus. A significant 75 % elevation in serum FFA levels was recorded post GH. Microarray identified 79 GH-regulated genes in muscle. With qRT-PCR we then examined the expression of selected genes in the presence and absence of glucose-induced suppression of lipolysis. Four genes involved in the JAK-STAT5 signaling pathway were regulated by GH, including SOCS1-3 and CISH, in addition to three genes associated with insulin action: NFkB1A, PIK3C2B, and PRKAG2. The gene encoding ANGPTL4, a protein involved in lipolysis and suppression of LPL activity, exhibited the most pronounced up regulation (5.6 fold) after GH, which was abrogated by concomitant suppression of lipolysis. The GH-induced stimulation of ANGPTL4 gene expression therefore seems secondary to induction of lipolysis. This new concept would imply that abundant supply of circulating FFA would decrease the need for alternative triglyceride derived FFA through distinct inhibition of LPL mediated by increased ANGPTL4 gene expression in human muscle.
OriginalsprogEngelsk
TidsskriftJournal of Lipid Research
Vol/bind54
Nummer7
Sider (fra-til)1988-1997
Antal sider10
ISSN0022-2275
DOI
StatusUdgivet - 20 jul. 2013

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