Mediation of the behavioral, endocrine and thermoregulatory actions of ghrelin

Jászberényi, Miklós; Bujdosó, E.; Bagosi, Zsolt; Telegdy, Gyula

doi:10.1016/j.yhbeh.2006.03.010

Cited by 52 publications

(43 citation statements)

References 47 publications

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“…Also, intracerebroventricular injection of ghrelin (19) and des-acyl ghrelin (58) increases spontaneous locomotor activity of rats. The effects of GHSs on sleep in other species are less consistent and dependent on the timing of the administration.…”

Section: Discussionmentioning

confidence: 99%

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Szentirmai¹,

Kapás²,

Krueger³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

109

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Szentirmai É , Kapás L, Krueger JM. Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats. Am J Physiol Regul Integr Comp Physiol 292: R575-R585, 2007. First published August 17, 2006; doi:10.1152/ajpregu.00448.2006.-Ghrelin, a gutbrain peptide, is best known for its role in the stimulation of feeding and growth hormone release. In the brain, orexin, neuropeptide Y (NPY), and ghrelin are parts of a food intake regulatory circuit. Orexin and NPY are also implicated in maintaining wakefulness. Previous experiments in our laboratory revealed that intracerebroventricular injections of ghrelin induce wakefulness in rats. To further elucidate the possible role of ghrelin in the regulation of arousal, we studied the effects of microinjections of ghrelin into hypothalamic sites, which are implicated in the regulation of feeding and sleep, such as the lateral hypothalamus (LH), medial preoptic area (MPA), and paraventricular nucleus (PVN) on sleep in rats. Sleep responses, motor activity, and food intake after central administration of 0.04, 0.2, or 1 g (12, 60, or 300 pmol) ghrelin were recorded. Microinjections of ghrelin into the LH had strong wakefulness-promoting effects lasting for 2 h. Wakefulness was also stimulated by ghrelin injection into the MPA and PVN; the effects were confined to the first hour after the injection. Ghrelin's non-rapid-eye-movement sleepsuppressive effect was accompanied by attenuation in the electroencephalographic (EEG) slow-wave activity and changes in the EEG power spectrum. Food consumption was significantly stimulated after microinjections of ghrelin into each hypothalamic site. Together, these results are consistent with the hypothesis that forebrain ghrelinergic mechanisms play a role in the regulation of vigilance, possibly through activating the components of the food intake-and arousalpromoting network formed by orexin and NPY. lateral hypothalamus; medial preoptic area; paraventricular nucleus; electroencephalogram; slow-wave activity; sleep GHRELIN IS A 28-AMINO ACID peptide produced by endocrine cells in the gastrointestinal system and by neurons in the central nervous system (21). Circulating ghrelin is derived mainly from the stomach (1). Plasma ghrelin levels inversely correlate with feeding; fasting increases, while food intake reduces, plasma ghrelin concentrations (7, 61). In the brain, ghrelin is produced by arcuate nucleus (ARC) neurons and by a distinct hypothalamic neuronal population in the internuclear region (6). Ghrelin's actions are mediated by the growth hormone secretagogue receptor (GHS-R) (21). GHS-R mRNA is widely distributed in the gastrointestinal tract, sensory vagus fibers, and the brain. Those hypothalamic nuclei that are implicated in the regulation of feeding and/or sleep-wake activity, such as the lateral hypothalamus (LH), paraventricular nucleus (PVN), ARC, dorsomedial hypothalamic nucleus, anteroventral preoptic nucleus, anterior hypothalamic area, suprachiasmatic nucleus, anterolateral hypothalamic nucleus, and the...

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Section: Discussionmentioning

confidence: 99%

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Szentirmai¹,

Kapás²,

Krueger³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

109

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“…Initial studies suggested a biphasic action of AG on thermogenesis, in that low doses of AG could reduce body temperature (Lawrence et al 2002), while high doses could increase it (Jaszberenyi et al 2006), probably through a hypothalamic action (Tokizawa et al 2012). This idea is supported by the fact that ghrelin gene KO mice cannot control body temperature under extreme thermic conditions (Szentirmai et al 2009), and because areas of the hypothalamus located in the vicinity of cold-sensitive neurons exhibit ghrelin-binding sites (Wiedmer et al 2011).…”

Section: Nonendocrine Actionsmentioning

confidence: 99%

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Gahete

Rincón-Fernández

Villa-Osaba

et al. 2013

Journal of Endocrinology

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Ghrelin is a 28-amino acid acylated hormone, highly expressed in the stomach, which binds to its cognate receptor (GHSR1a) to regulate a plethora of relevant biological processes, including food intake, energy balance, hormonal secretions, learning, inflammation, etc. However, ghrelin is, in fact, the most notorious component of a complex, intricate regulatory system comprised of a growing number of alternative peptides (e.g. obestatin, unacylated ghrelin, and In1-ghrelin, etc.), known (GHSRs) and, necessarily unknown receptors, as well as modifying enzymes (e.g. ghrelin-O-acyl-transferase), which interact among them as well as with other regulatory systems in order to tightly modulate key (patho)-physiological processes. This multiplicity of functions and versatility of the ghrelin system arise from a dual, genetic and functional, complexity. Importantly, a growing body of evidence suggests that dysregulation in some of the components of the ghrelin system can lead to or influence the development and/or progression of highly concerning pathologies such as endocrine-related tumors, inflammatory/cardiovascular diseases, and neurodegeneration, wherein these altered components could be used as diagnostic, prognostic, or therapeutic targets. In this context, the aim of this review is to integrate and comprehensively analyze the multiple components and functions of the ghrelin system described to date in order to define and understand its biological and (patho)-physiological significance.

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“…Baseline food intake (Gilg and Lutz, 2006) and dietary patterns with high protein or liquid intake (Blom et al, 2006) may influence ghrelin regulation. Drugs for symptom control (eg, haloperidol (Jaszberenyi et al, 2006), 5-HT-3 antagonist ) may interact with ghrelin metabolism. Patients often have enhanced levels of proinflammatory cytokines and stress, which are reported to increase preprandial activation of ghrelin secretion (Kristenssson et al, 2006) by activation of sympathetic nerves but not by epinephrine (Mundinger et al, 2006).…”

Section: Intravenous Ghrelin For Cancer Anorexia/cachexia F Strasser mentioning

confidence: 99%

“…The limitations of this study design include the lack of chronic efficacy data beyond two weekly infusions; namely, body composition (lean body mass, fat mass (Theander-Carrillo et al, 2006)), objective subconscious locomotive motor and physical activity (Jaszberenyi et al, 2006), energy expenditure measurements (Lejeune et al, 2006), and gastrointestinal motility (Binn et al, 2006;Blom et al, 2006). Our results on dose responsiveness may be influenced by unbalanced groups: UD patients had more metastases, greater weight loss, lower dietary intake, more early satiety, and were closer to death.…”

Section: Intravenous Ghrelin For Cancer Anorexia/cachexia F Strasser mentioning

confidence: 99%

Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study

Strasser¹,

et al. 2008

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Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 and placebo on days 4 and 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2 mg kg À1 (lower-dose) ghrelin; 11 received 8 mg kg À1 (upper-dose) ghrelin. Active and total ghrelin, growth hormone (GH), and insulin-like growth factor 1 levels were monitored at baseline (4 -5 days before day 1), during treatment days, and at end of study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria and cardiac examination) did not differ between ghrelin and placebo. No grade 3/4 toxicity or stimulation of tumour growth was observed. The peak increase of GH, a biological marker of ghrelin action, was 25 ng ml À1 with lower-dose and 42 ng ml À1 with upper-dose ghrelin. Morning fasting total ghrelin levels were higher (Po0.05) for upper-dose patients at end of study (3580 pg ml À1 ) than at baseline (990 pg ml À1 ). Insulin-like growth factor 1 levels did not change. At day 8, 81% of patients preferred ghrelin to placebo as against 63% at the end of study. Nutritional intake and eating-related symptoms, measured to explore preliminary efficacy, did not differ between ghrelin and placebo. Ghrelin is well tolerated and safe in patients with advanced cancer. For safety, tolerance, and patients' preference for treatment, no difference was observed between the lower-and upper-dose group.

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Mediation of the behavioral, endocrine and thermoregulatory actions of ghrelin

Cited by 52 publications

References 47 publications

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study

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