Gene expression in skeletal muscle after an acute intravenous GH bolus in human subjects: identification of a mechanism regulating ANGPTL4

Clasen, Berthil Frederik Forrest; Krusenstjerna-Hafstrøm, Thomas; Vendelbo, Mikkel Holm; Thorsen, Kasper; Escande, Carlos; Møller, Niels; Pedersen, Steen B.; Jørgensen, Jens Otto Lunde; Jessen, Niels

doi:10.1194/jlr.p034520

Cited by 22 publications

(16 citation statements)

References 47 publications

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“…Notably, stimulation with GH does not increase lipolysis in explants of human AT (Fain et al 2008) or isolated human adipocytes (Marcus et al 1994), but the sensitivity toward b-adrenergic agonists is enhanced by the presence of GH in the culture medium (Marcus et al 1994). In line with this, it has recently been demonstrated that GH administration in human subjects increases ANGPTL4 levels in plasma (Clasen et al 2013). Given the permissive effect of this protein on cAMP-mediated lipolysis, it seems likely that elevations in systemic ANGPTL4 levels could be one of the mechanisms by which GH stimulates AT lipolysis.…”

Section: Growth Hormonementioning

confidence: 74%

Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease

Nielsen¹,

Jessen²,

Jørgensen³

et al. 2014

Journal of Molecular Endocrinology

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300

239

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Lipolysis is the process by which triglycerides (TGs) are hydrolyzed to free fatty acids (FFAs) and glycerol. In adipocytes, this is achieved by sequential action of adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase. The activity in the lipolytic pathway is tightly regulated by hormonal and nutritional factors. Under conditions of negative energy balance such as fasting and exercise, stimulation of lipolysis results in a profound increase in FFA release from adipose tissue (AT). This response is crucial in order to provide the organism with a sufficient supply of substrate for oxidative metabolism. However, failure to efficiently suppress lipolysis when FFA demands are low can have serious metabolic consequences and is believed to be a key mechanism in the development of type 2 diabetes in obesity. As the discovery of ATGL in 2004, substantial progress has been made in the delineation of the remarkable complexity of the regulatory network controlling adipocyte lipolysis. Notably, regulatory mechanisms have been identified on multiple levels of the lipolytic pathway, including gene transcription and translation, post-translational modifications, intracellular localization, protein-protein interactions, and protein stability/ degradation. Here, we provide an overview of the recent advances in the field of AT lipolysis with particular focus on the molecular regulation of the two main lipases, ATGL and HSL, and the intracellular and extracellular signals affecting their activity.

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Section: Growth Hormonementioning

confidence: 74%

Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease

Nielsen¹,

Jessen²,

Jørgensen³

et al. 2014

Journal of Molecular Endocrinology

Self Cite

300

239

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“…However, manipulating hematocrit levels within the physiologically relevant limits in humans did not lead to significant alterations in gene expression, even though we covered a broad spectrum of possible physiological changes. The method we used (Human Gene 1.0 ST Array) detected altered skeletal muscle gene expression 120 minutes after growth hormone treatment and after 72‐hour fasting (Vendelbo et al ., unpublished data), thus validating the method.…”

Section: Discussionmentioning

confidence: 99%

Prolonged erythropoietin treatment does not impact gene expression in human skeletal muscle

et al. 2015

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“…In addition it has been reported that GH increases phosphorylation of STAT-5b in human muscle and fat (8) and activates SOCS1-3, CISH, and IGF1 mRNA expression in skeletal muscle (4,9,10). Stress conditions such as exercise and fasting with increased GH secretion have also been shown to stimulate human skeletal muscle STAT-5b phosphorylation and IGF1 mRNA expression (11,12), although it is unclear whether this involves stimulation of SOCS/CISH transcription.…”

Section: Introductionmentioning

confidence: 99%

“…In adipocytes and skeletal muscle, STAT-5b serves as a transcription factor for target genes including a family of cytokine-inducible suppressors of cytokine signaling (SOCS) (1,2,3), cytokine inducible SH2-containing protein (CISH) (2,4), and insulin-like growth factor 1 (IGF1). GH has important actions to regulate anabolic signals and preserve lean body mass protein (1); some of these anabolic effects are mediated by stimulation of lipolysis (5,6).…”

Section: Introductionmentioning

confidence: 99%

GH signaling in human adipose and muscle tissue during ‘feast and famine’: amplification of exercise stimulation following fasting compared to glucose administration

Vendelbo

Christensen

Grønbæk

et al. 2015

European Journal of Endocrinology

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Objective: Fasting and exercise stimulates, whereas glucose suppresses GH secretion, but it is uncertain how these conditions impact GH signaling in peripheral tissues. To test the original 'feast and famine hypothesis' by Rabinowitz and Zierler, according to which the metabolic effects of GH are predominant during fasting, we specifically hypothesized that fasting and exercise act in synergy to increase STAT-5b target gene expression. Design and methods: Eight healthy men were studied on two occasions in relation to a 1 h exercise bout: i) with a concomitant i.v. glucose infusion ('feast') and ii) after a 36 h fast ('famine'). Muscle and fat biopsy specimens were obtained before, immediately after, and 30 min after exercise. Results: GH increased during exercise on both examination days and this effect was amplified by fasting, and free fatty acid (FFA) levels increased after fasting. STAT-5b phosphorylation increased similarly following exercise on both occasions. In adipose tissue, suppressors of cytokine signaling 1 (SOCS1) and SOCS2 were increased after exercise on the fasting day and both fasting and exercise increased cytokine inducible SH2-containing protein (CISH). In muscle, SOCS2 and CISH mRNA were persistently increased after fasting. Muscle SOCS1, SOCS3, and CISH mRNA expression increased, whereas SOCS2 decreased after exercise on both examination days. Conclusions: This study demonstrates that fasting and exercise act in tandem to amplify STAT-5b target gene expression (SOCS and CISH) in adipose and muscle tissue in accordance with the 'feast and famine hypothesis'; the adipose tissue signaling responses, which hitherto have not been scrutinized, may play a particular role in promoting FFA mobilization.

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Gene expression in skeletal muscle after an acute intravenous GH bolus in human subjects: identification of a mechanism regulating ANGPTL4

Cited by 22 publications

References 47 publications

Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease

Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease

Prolonged erythropoietin treatment does not impact gene expression in human skeletal muscle

GH signaling in human adipose and muscle tissue during ‘feast and famine’: amplification of exercise stimulation following fasting compared to glucose administration

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