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Journal ArticleDOI

Exercise-induced suppression of acylated ghrelin in humans

01 Jun 2007-Journal of Applied Physiology (American Physiological Society)-Vol. 102, Iss: 6, pp 2165-2171
TL;DR: It is demonstrated that plasma acylated ghrelin concentration and hunger are suppressed during running.
Abstract: Ghrelin is an orexigenic hormone secreted from endocrine cells in the stomach and other tissues. Acylation of ghrelin is essential for appetite regulation. Vigorous exercise induces appetite suppre...

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01 Nov 2004
TL;DR: Ghrelin infusion increased food intake in obese as well as lean subjects as discussed by the authors, and increased palatability of food in the obese group only (mean increase 36.6±9.4%, P<0.01 in both cases.)
Abstract: OBJECTIVE:To investigate whether effects on food intake are seen in obese subjects receiving exogenous administration of ghrelin.DESIGN:Randomised, double-blind, placebo-controlled study of intravenous ghrelin at doses 1 pmol/kg/min and 5 pmol/kg/min.SUBJECTS:In all, 12 healthy lean subjects (mean body mass index (BMI) 20.5±0.17 kg/m2) and 12 healthy overweight and obese subjects (mean BMI 31.9±1.02 kg/m2).MEASUREMENTS:Food intake, appetite and palatability of food, ghrelin and other obesity-related hormones, growth hormone.RESULTS:Low-dose infusion of ghrelin increased ad libitum energy intake at a buffet meal in the obese group only (mean increase 36.6±9.4%, P<0.01.) High-dose ghrelin infusion increased energy intake in both groups (mean increase 20.1±10.6% in the lean and 70.1±15.5% in the obese, P<0.01 in both cases.) Ghrelin infusion increased palatability of food in the obese group.CONCLUSION:Ghrelin increases food intake in obese as well as lean subjects. Obese people are sensitive to the appetite-stimulating effects of ghrelin and inhibition of circulating ghrelin may be a useful therapeutic target in the treatment of obesity.

351 citations

Journal ArticleDOI
TL;DR: The findings suggest ghrelin and PYY may regulate appetite during and after exercise, but further research is required to establish whether exercise-induced changes in ghrel in and peptide YY influence subsequent food intake.
Abstract: Resistance (muscle strengthening) exercise is a key component of exercise recommendations for weight control, yet very little is known about the effects of resistance exercise on appetite. We investigated the effects of resistance and aerobic exercise on hunger and circulating levels of the gut hormones acylated ghrelin and peptide YY (PYY). Eleven healthy male students: age 21.1 +/- 0.3 yr, body mass index 23.1 +/- 0.4 kg/m(2), maximum oxygen uptake 62.1 +/- 1.8 ml.kg(-1).min(-1) (means +/- SE) undertook three, 8-h trials, 1) resistance exercise: a 90-min free weight lifting session followed by a 6.5-h rest period, 2) aerobic exercise: a 60-min run followed by a 7-h rest period, 3) control: an 8-h rest, in a randomized crossover design. Meals were provided 2 and 5 h into each trial. Hunger ratings and plasma concentrations of acylated ghrelin and PYY were measured throughout. Two-way ANOVA revealed significant (P < 0.05) interaction effects for hunger, acylated ghrelin, and PYY, indicating suppressed hunger and acylated ghrelin during aerobic and resistance exercise and increased PYY during aerobic exercise. A significant trial effect was observed for PYY, indicating higher concentrations on the aerobic exercise trial than the other trials (8 h area under the curve: control 1,411 +/- 110, resistance 1,381 +/- 97, aerobic 1,750 +/- 170 pg/ml 8 h). These findings suggest ghrelin and PYY may regulate appetite during and after exercise, but further research is required to establish whether exercise-induced changes in ghrelin and PYY influence subsequent food intake.

318 citations


Cites background or methods or result from "Exercise-induced suppression of acy..."

  • ...Recently, we have shown that plasma acylated ghrelin is suppressed during vigorous treadmill running (9), while another recent study has reported increases in acylated ghrelin after five consecutive days of aerobic exercise (1 h/day) (36)....

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  • ...The finding that hunger is suppressed during and immediately after vigorous treadmill running is consistent with previous studies indicating that strenuous (around 60% of maximum oxygen uptake and above) aerobic exercise transiently suppresses appetite (6, 9, 29, 39)....

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  • ...Subjects completed a 16-min submaximal treadmill running test and a maximum oxygen uptake test on a motorized treadmill, as described previously (9)....

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  • ...Expired air samples were collected into Douglas bags during these tests for the determination of oxygen consumption and carbon dioxide production (9)....

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  • ...Oxygen consumption and carbon dioxide production were determined from expired air samples, as described previously (9)....

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Journal ArticleDOI
TL;DR: Current experiments indicate that circadian misalignment has an adverse effect on metabolic and hormonal factors such as circulating glucose and insulin, and further research is needed to determine the underlying mechanisms that cause the negative effects induced by circadian misAlignment.

318 citations


Cites background from "Exercise-induced suppression of acy..."

  • ...Furthermore, daytime exercise is known to suppress concentrations of the ‘hunger hormone’ acylated ghrelin (Broom et al., 2007)....

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Journal ArticleDOI
TL;DR: It is hypothesized that the beneficial impact of exercise can contribute to its well-established efficacy in the prevention of weight regain in obese individuals, however, more studies are needed in the obese population to clearly establish the role of exercise on appetite control.
Abstract: In this review, we discuss the role of inactivity and exercise on appetite regulation, both in the short and long term, and the potential mechanisms involved. A better short-term appetite control has been described in active compared to sedentary men, and an exercise intervention was shown to improve appetite control in previously sedentary individuals. The mechanisms whereby exercise improves short-term appetite control remain obscure and although the changes in the postprandial release of satiety peptides are attractive hypotheses, it remains unproven. The impact of exercise on habitual food intake is also controversial and likely to be dependent on restraint level and body weight. We hypothesize that the beneficial impact of exercise on appetite regulation can contribute to its well-established efficacy in the prevention of weight regain in obese individuals. However, more studies are needed in the obese population to clearly establish the role of exercise on appetite control in this group.

267 citations

Journal ArticleDOI
TL;DR: Highly expressed and enriched 7TM receptors and associated Gα subunits constitute a major part of the molecular machinery directly mediating neuronal and endocrine stimulation versus metabolite and somatostatin inhibition of ghrelin secretion including a series of novel receptor targets not previously identified on the gh Relin cell.
Abstract: The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively identified and functionally characterized using in vitro, ex vivo and in vivo methods. Five Gαs-coupled receptors efficiently stimulated ghrelin secretion: as expected the β1-adrenergic, the GIP and the secretin receptors but surprisingly also the composite receptor for the sensory neuropeptide CGRP and the melanocortin 4 receptor. A number of Gαi/o-coupled receptors inhibited ghrelin secretion including somatostatin receptors SSTR1, SSTR2 and SSTR3 and unexpectedly the highly enriched lactate receptor, GPR81. Three other metabolite receptors known to be both Gαi/o- and Gαq/11-coupled all inhibited ghrelin secretion through a pertussis toxin-sensitive Gαi/o pathway: FFAR2 (short chain fatty acid receptor; GPR43), FFAR4 (long chain fatty acid receptor; GPR120) and CasR (calcium sensing receptor). In addition to the common Gα subunits three non-common Gαi/o subunits were highly enriched in ghrelin cells: GαoA, GαoB and Gαz. Inhibition of Gαi/o signaling via ghrelin cell-selective pertussis toxin expression markedly enhanced circulating ghrelin. These 7TM receptors and associated Gα subunits constitute a major part of the molecular machinery directly mediating neuronal and endocrine stimulation versus metabolite and somatostatin inhibition of ghrelin secretion including a series of novel receptor targets not previously identified on the ghrelin cell.

260 citations


Cites background from "Exercise-induced suppression of acy..."

  • ...However, much higher plasma concentrations of lactate are obtained during exercise (up to 25 mM) [57], and plasma ghrelin levels are suppressed during acute exercise [102–105]....

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References
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Journal ArticleDOI
09 Dec 1999-Nature
TL;DR: The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelIn, a peptide specifically releases GH both in vivo and in vitro.
Abstract: Small synthetic molecules called growth-hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through GHS-R, a G-protein-coupled receptor for which the ligand is unknown. Recent cloning of GHS-R strongly suggests that an endogenous ligand for the receptor does exist and that there is a mechanism for regulating GH release that is distinct from its regulation by hypothalamic growth-hormone-releasing hormone (GHRH). We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. The purified ligand is a peptide of 28 amino acids, in which the serine 3 residue is n-octanoylated. The acylated peptide specifically releases GH both in vivo and in vitro, and O-n-octanoylation at serine 3 is essential for the activity. We designate the GH-releasing peptide 'ghrelin' (ghre is the Proto-Indo-European root of the word 'grow'). Human ghrelin is homologous to rat ghrelin apart from two amino acids. The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin.

8,073 citations


"Exercise-induced suppression of acy..." refers background in this paper

  • ...Acylation is thought to be essential for ghrelin to bind to the growth hormone-secretagogue receptor and to cross the blood-brain barrier (29, 36)....

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  • ...GHRELIN IS A 28-AMINO ACID peptide hormone that stimulates the release of growth hormone from the pituitary (29)....

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Journal Article
TL;DR: This stately book is to show how the various types of animals have solved the fundamental problems of life, and how their struc-ture is to be interpreted in terms of their functions and environment.
Abstract: THE aim of this stately book is to show how the various types of animals have solved the fundamental problems of life, and how their struc-ture is to be interpreted in terms of their functions and environment. The keynote of the book is to keep the gratufate the author on the success of his for he has written a worthy successor to the once-famous, now forgotten “Anatomischphysiologische Uebersicht des Tierreiches,” by Bergmann and Leuckart. The outstanding merit of the achievement is in its unified or synthetic presentation of the facts—it is at once anatomical and physiological, cecological and evolutionist. This general biological outlook is very useful for the analytic student.

4,072 citations

Journal ArticleDOI
TL;DR: Changes in PV calculated from the increase in plasma protein concentration averaged 7.5(z compared with 12.2 y0 calculated from changes in Hb and Hct, the difference could be accounted for by a loss of 6v10 plasma protein from the circulation.
Abstract: DILL, D. B., AND I>. L. &STILL. Calculation of pcrccntage changes in volumes of blood, plasma, and red cells in dehydration. J. Appl. Physiol. 37(2): 247-248. 1974.-Observations on hematocrit (Hct) and hemoglobin (Hb) were Inade in six men before and after running long enough to cause a 4y0 decrease in body weight. Subscripts B and A were used to denote before dehydration and after dehydration, respectively. Relations were derived between BVn, BVA, Hbn, HbA, Hctg, and HctA with which one can calculate the percentage decreases in BV, CV, and PV, as well as the concentration of hemoglobin in red cells, g. 100 ml-l (MCHC). When subjects reach the same level of dehydration the water loss from the various body compartments may vary reflecting difference in salt losses in sweat. Changes in PV calculated from the increase in plasma protein concentration averaged 7.5(z compared with 12.2 y0 calculated from changes in Hb and Hct. The difference could be accounted for by a loss of 6v10 plasma protein from the circulation.

3,405 citations


"Exercise-induced suppression of acy..." refers methods in this paper

  • ...These were used to calculate changes in plasma volume (15)....

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Journal ArticleDOI
11 Jan 2001-Nature
TL;DR: It is shown that ghrelin is involved in the hypothalamic regulation of energy homeostasis and probably has a function in growth regulation by stimulating feeding and release of growth hormone.
Abstract: Ghrelin is an acylated peptide that stimulates the release of growth hormone from the pituitary. Ghrelin-producing neurons are located in the hypothalamus, whereas ghrelin receptors are expressed in various regions of the brain, which is indicative of central-and as yet undefined-physiological functions. Here we show that ghrelin is involved in the hypothalamic regulation of energy homeostasis. Intracerebroventricular injections of ghrelin strongly stimulated feeding in rats and increased body weight gain. Ghrelin also increased feeding in rats that are genetically deficient in growth hormone. Anti-ghrelin immunoglobulin G robustly suppressed feeding. After intracerebroventricular ghrelin administration, Fos protein, a marker of neuronal activation, was found in regions of primary importance in the regulation of feeding, including neuropeptide Y6 (NPY) neurons and agouti-related protein (AGRP) neurons. Antibodies and antagonists of NPY and AGRP abolished ghrelin-induced feeding. Ghrelin augmented NPY gene expression and blocked leptin-induced feeding reduction, implying that there is a competitive interaction between ghrelin and leptin in feeding regulation. We conclude that ghrelin is a physiological mediator of feeding, and probably has a function in growth regulation by stimulating feeding and release of growth hormone.

3,400 citations


"Exercise-induced suppression of acy..." refers result in this paper

  • ...This suggestion is supported by the findings that intracerebroventricular ghrelin administration stimulates feeding in rats (37, 51) and that intravenous ghrelin infusion increases food intake in humans (16, 50)....

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Journal ArticleDOI
01 Aug 2001-Diabetes
TL;DR: The hypothesis that ghrelin plays a physiological role in meal initiation in humans is supported by the clear preprandials rise and postprandial fall in plasma ghrelIn levels.
Abstract: The recently discovered orexigenic peptide ghrelin is produced primarily by the stomach and circulates in blood at levels that increase during prolonged fasting in rats. When administered to rodents at supraphysiological doses, ghrelin activates hypothalamic neuropeptide Y/agouti gene-related protein neurons and increases food intake and body weight. These findings suggest that ghrelin may participate in meal initiation. As a first step to investigate this hypothesis, we sought to determine whether circulating ghrelin levels are elevated before the consumption of individual meals in humans. Ghrelin, insulin, and leptin were measured by radioimmunoassay in plasma samples drawn 38 times throughout a 24-h period in 10 healthy subjects provided meals on a fixed schedule. Plasma ghrelin levels increased nearly twofold immediately before each meal and fell to trough levels within 1 h after eating, a pattern reciprocal to that of insulin. Intermeal ghrelin levels displayed a diurnal rhythm that was exactly in phase with that of leptin, with both hormones rising throughout the day to a zenith at 0100, then falling overnight to a nadir at 0900. Ghrelin levels sampled during the troughs before and after breakfast correlated strongly with 24-h integrated area under the curve values (r = 0.873 and 0.954, respectively), suggesting that these convenient, single measurements might serve as surrogates for 24-h profiles to estimate overall ghrelin levels. Circulating ghrelin also correlated positively with age (r = 0.701). The clear preprandial rise and postprandial fall in plasma ghrelin levels support the hypothesis that ghrelin plays a physiological role in meal initiation in humans.

2,869 citations


"Exercise-induced suppression of acy..." refers background or result in this paper

  • ...Plasma ghrelin concentrations rise before meals and decrease following meals, suggesting that ghrelin is orexigenic (appetite stimulating) (12, 13)....

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  • ...This is consistent with data from studies examining the response to feeding of both plasma acylated ghrelin (1, 3, 17, 23, 34) and plasma total ghrelin (3, 12, 13, 23, 34)....

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