title: Gene expression in skeletal muscle after an acute intravenous GH bolus in human subjects: identification of a mechanism regulating ANGPTL4.
abstract: Growth hormone (GH) acutely stimulates lipolysis and fat oxidation, a process that 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: NFκB1A, PIK3C2B, and PRKAG2. The gene encoding ANGPTL4, a protein involved in lipolysis and suppression of LPL activity, exhibited the most pronounced upregulation (5.6-fold) after GH, which was abrogated by concomitant suppression of lipolysis. Therefore, the GH-induced stimulation of ANGPTL4 gene expression seems secondary to induction of lipolysis. This new concept implies that abundant supply of circulating FFA decreases the need for alternative triglyceride-derived FFA through distinct inhibition of LPL mediated by increased ANGPTL4 gene expression in human muscle.
authors.affiliation: Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Berthil F F
authors.initials: BF
authors.lastname: Clasen
authors.forename: Thomas
authors.initials: T
authors.lastname: Krusenstjerna-Hafstrøm
authors.forename: Mikkel Holm
authors.initials: MH
authors.lastname: Vendelbo
authors.forename: Kasper
authors.initials: K
authors.lastname: Thorsen
authors.forename: Carlos
authors.initials: C
authors.lastname: Escande
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Jens Otto L
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
mesh_terms: D061605:Administration, Intravenous; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D013006:Growth Hormone / Q000008:administration & dosage* / Q000494:pharmacology*; D006801:Humans; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D013006:Growth Hormone
keywords: angiopoietin-related protein-like 4; growth hormone; human gene array; lipid metabolism