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Acute peripheral metabolic effects of intraarterial ghrelin infusion in healthy young men.

ABSTRACT: Ghrelin is the endogenous agonist for the growth hormone secretagogue receptor (GHS-R). Intravenous administration of ghrelin induces insulin resistance and hyperglycemia and increases the levels of free fatty acids (FFA).To investigate whether these effects are mediated directly by ghrelin in skeletal muscle tissue.This study was single blinded, randomized, and placebo controlled. Eight healthy men (25.5 ± 3.1 years) received 240 min of intraarterial ghrelin infusion (4.2 ng × kg(-1) × min(-1)) into one femoral artery and intraarterial placebo infusion into the contralateral artery. Simultaneous blood samples were drawn from both femoral veins and muscle biopsies were obtained from both legs during both a basal period and during a hyperinsulinemic and euglycemic clamp period.Ghrelin significantly elevated venous FFA levels and venous dilution of palmitate, suggestive of increased lipolysis. Glucose metabolism was unchanged, and there were no direct effects on pertinent enzymes in the insulin signaling cascade. The metabolic clearance rate of acyl ghrelin was 12.5 ± 3.3 ml × kg(-1) × min(-1). Acyl and desacyl ghrelin levels both increased.The results of this study suggest that ghrelin may stimulate lipolysis directly in skeletal muscle.

SUBMITTER: Vestergaard ET

PROVIDER: S-EPMC5393419 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Acute peripheral metabolic effects of intraarterial ghrelin infusion in healthy young men.

Vestergaard Esben Thyssen ET Buhl Mads M Gjedsted Jakob J Madsen Michael M Jessen Niels N Nielsen Soren S Gaylinn Bruce D BD Liu Jianhua J Thorner Michael O MO Moller Niels N Jorgensen Jens Otto Lunde JO

The Journal of clinical endocrinology and metabolism 20101117 2

<h4>Context</h4>Ghrelin is the endogenous agonist for the growth hormone secretagogue receptor (GHS-R). Intravenous administration of ghrelin induces insulin resistance and hyperglycemia and increases the levels of free fatty acids (FFA).<h4>Objective</h4>To investigate whether these effects are mediated directly by ghrelin in skeletal muscle tissue.<h4>Design</h4>This study was single blinded, randomized, and placebo controlled. Eight healthy men (25.5 ± 3.1 years) received 240 min of intraarte ...[more]

PMID: 21084392

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Project description:BackgroundSevere energy deficits cause interrelated reductions in testosterone and fat free mass. Testosterone supplementation may mitigate those decrements, but could also reduce circulating concentrations of the orexigenic hormone ghrelin, thereby exacerbating energy deficit by suppressing appetite.ObjectiveTo determine whether testosterone supplementation during severe energy deficit influences fasting and postprandial ghrelin concentrations and appetite.Design and methodsSecondary analysis of a randomized, double-blind trial that determined the effects of testosterone supplementation on body composition changes during and following severe energy deficit in nonobese, eugonadal men. Phase 1 (PRE-ED): 14-day run-in; phase 2: 28 days, 55% energy deficit with 200 mg testosterone enanthate weekly (TEST; n = 24) or placebo (PLA; n = 26); phase 3: free-living until body mass recovered (end-of-study; EOS). Fasting and postprandial acyl ghrelin and des-acyl ghrelin concentrations and appetite were secondary outcomes measured during the final week of each phase.ResultsFasting acyl ghrelin concentrations, and postprandial acyl and des-acyl ghrelin concentrations increased in PLA during energy deficit then returned to PRE-ED values by EOS, but did not change in TEST (phase-by-group, P < 0.05). Correlations between changes in free testosterone and changes in fasting acyl ghrelin concentrations during energy deficit (ρ = -0.42, P = 0.003) and body mass recovery (ρ = -0.38; P = 0.01) were not mediated by changes in body mass or body composition. Transient increases in appetite during energy deficit were not affected by testosterone treatment.ConclusionsTestosterone supplementation during short-term, severe energy deficit in healthy men prevents deficit-induced increases in circulating ghrelin without blunting concomitant increases in appetite.Clinical trials registrationwww.clinicaltrials.gov NCT02734238 (registered 12 April 2016).

Dataset Information

Acute peripheral metabolic effects of intraarterial ghrelin infusion in healthy young men.

Publications

Acute peripheral metabolic effects of intraarterial ghrelin infusion in healthy young men.

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