Abstract
BackgroundThe increase in growth hormone (GH) secretion during a prolonged fast stimulates lipolytic rate, thereby augmenting the mobilization of endogenous energy at a time when fuel availability is very low.Study aimTo identify the specific component of GH secretory pattern responsible for the stimulation of lipolytic rate during fasting in humans.Study protocolWe measured lipolytic rate (using stable isotope dilution technique) after an overnight fast in 15 young, healthy, non-obese subjects (11 men and 4 women), and again on four separate occasions after a 59 h fast. These four prolonged fasting trials differed only by the contents of an infusion solution provided throughout the 59 h fasting period. Subjects were infused either with normal saline (“Control”; n = 15) or with graded doses of a GH Releasing Hormone Receptor Antagonist (GHRHa):10 μg/kg/h (“High”; n = 15), 1 μg /kg/h (“Medium”; n = 8), or 0.5 μg /kg/h (“Low”; n = 6).ResultsAs expected, the 59 h fast completely suppressed plasma insulin levels and markedly increased endogenous GH concentrations (12 h vs 59 h Fast; p = 0.0044). Administration of GHRHa induced dose-dependent reduction in GH concentrations in response to the 59 h fast (p < 0.05). We found a strong correlation between the rate of lipolysis and GH mean peak amplitude (R = 0.471; p = 0.0019), and total GH pulse area under the curve (AUC) (R = 0.49; p = 0.0015), but not the GH peak frequency (R = 0.044; p = 0.8) or interpulse GH concentrations (R = 0.25; p = 0.115).ConclusionDuring prolonged fasting (i.e., 2–3 days), when insulin secretion is abolished, the pulsatile component of GH secretion becomes a key metabolic regulator of the increase in lipolytic rate.
Highlights
Growth hormone (GH) has major effects on metabolic processes in humans [1,2,3,4,5]
We found a strong correlation between the rate of lipolysis and growth hormone (GH) mean peak amplitude (R = 0.471; p = 0.0019), and total GH pulse area under the curve (AUC) (R = 0.49; p = 0.0015), but not the GH peak frequency (R = 0.044; p = 0.8) or interpulse GH concentrations (R = 0.25; p = 0.115)
We have shown that GH Releasing Hormone Receptor Antagonist (GHRHa) was capable of suppressing mean daily GH concentrations in healthy non-obese subjects to ~ 70% both in the fed and fasting state [8]
Summary
Growth hormone (GH) has major effects on metabolic processes in humans [1,2,3,4,5]. Traditionally, the role of GH in human metabolism was determined by infusing GH to patients with GH deficiency, mostly to patients with panhypopituitarism [1,2,3,4,5]. There is an interplay between GH and insulin in their respective functions as regulators of lipolysis: GH is lipolytic and insulin is antilpolytic hormone We have previously shown that the lipolytic effect of GH is expressed when insulin secretion is diminished, i.e. during fasting state [8] This has major implication in the context of energy availability during starvation and/or other prolonged episodes of low caloric intake. Study protocol: We measured lipolytic rate (using stable isotope dilution technique) after an overnight fast in 15 young, healthy, non-obese subjects (11 men and 4 women), and again on four separate occasions after a 59 h fast These four prolonged fasting trials differed only by the contents of an infusion solution provided throughout the 59 h fasting period.
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