Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020175 (hunger)
 5,670 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The increasing prevalence of obesity and the obesity-associated morbidities represent one of the major health problems of the western society. This has renewed interest in our understanding of factors that control appetite. The 28 amino acid peptide may represent one of the key players in the regulation of food intake since it is the only circulating orexigenic peptide. Ghrelin not only acts as a hunger signal but also as an adiposity signal. These effects are influenced by the internal energy status and can be considered as homeostatic signals. In addition ghrelin has direct effects on components of the reward system and increases the appetitive value of food. This hedonic feeding behavior of ghrelin can be considered as a non-homeostatic signal as it occurs in the absence of nutritional or caloric deficiency. In this review we address how these signals, elicited by ghrelin, can powerfully augment the drive to eat. Better understanding of the mechanisms by which ghrelin exerts its effect may enable the development of new treatments for obesity but also for conditions of cachexia.
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PMID:Targeting the ghrelin receptor to regulate food intake. 1936 79

Malnutrition is a common complication in patients on dialysis and is strongly associated with poor prognosis. Effective therapy could substantially improve morbidity and mortality, but neither enteral nor parenteral supplementation provide long-term benefit because of the strong appetite suppression seen in such patients. We performed a double-blinded randomized crossover study of a week-long treatment with daily subcutaneous ghrelin, a gut hormone that regulates hunger through the hypothalamus, in a group of 12 malnourished dialysis patients. Ghrelin administration increased ghrelin levels in circulation, modestly reduced blood pressure for up to 2 h, and immediately and significantly increased appetite, with an increase in energy intake noted at the first study meal. Persistence of this effect throughout the week was confirmed with food diaries and final study meals. Energy expenditure, measured with free-living pulse and motion monitors, was unchanged by ghrelin. Our study shows that daily treatment with ghrelin achieves a sustained positive change in energy balance in malnourished dialysis patients. Direct manipulation of appetite with ghrelin or its analogs represents an attractive and promising therapeutic strategy for this difficult clinical problem.
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PMID:Sustained appetite improvement in malnourished dialysis patients by daily ghrelin treatment. 1956 55

Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. Mammalian target of rapamycin (mTOR) is an intracellular fuel sensor critical for cellular energy homeostasis. Here we showed the reciprocal relationship of gastric mTOR signaling and ghrelin during changes in energy status. mTOR activity was down-regulated, whereas gastric preproghrelin and circulating ghrelin were increased by fasting. In db/db mice, gastric mTOR signaling was enhanced, whereas gastric preproghrelin and circulating ghrelin were decreased. Inhibition of the gastric mTOR signaling by rapamycin stimulated the expression of gastric preproghrelin and ghrelin mRNA and increased plasma ghrelin in both wild-type and db/db mice. Activation of the gastric mTOR signaling by l-leucine decreased the expression of gastric preproghrelin and the level of plasma ghrelin. Overexpression of mTOR attenuated ghrelin promoter activity, whereas inhibition of mTOR activity by overexpression of TSC1 or TSC2 increased its activity. Ghrelin receptor antagonist d-Lys-3-GH-releasing peptide-6 abolished the rapamycin-induced increment in food intake despite that plasma ghrelin remained elevated. mTOR is therefore a gastric fuel sensor whose activity is linked to the regulation of energy intake through ghrelin.
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PMID:Gastric mammalian target of rapamycin signaling regulates ghrelin production and food intake. 1940 39

Motilin is a hormone released by the endocrine cells of the duodenal mucosa during fasting to stimulate gastrointestinal motility. Ghrelin, the closest family member of motilin, was discovered 10 years ago from the rat stomach as the long-awaited endogenous ligand of the growth hormone secretagogue receptor. Ghrelin has now emerged as a multifunctional hormone with important effects on energy homeostasis but also on gastrointestinal motility. Like motilin, it induces hunger contractions in the fasting state and acts postprandially to accelerate gastric emptying. While the development of motilin agonists for the treatment of hypomotility disorders has been going on for more than 15 years, the development of ghrelin agonists is still in its infancy. The failure of the first generation of motilin agonists in clinical trials has been largely due to problems of desensitization and worsening of symptoms due to effects on gastric accommodation. These issues are being taken care of with the second generation of motilin agonists that are currently under evaluation. Ghrelin agonists have the same potential as motilin agonists to treat hypomotility disorders but their effects on appetite may even be a bonus to treat disorders such as functional dyspepsia while ghrelin's anti-inflammatory effects may make it superior to motilin to treat post-operative ileus. Nevertheless the important endocrine activities of ghrelin may result in side effects which are not encountered with motilin. Future studies will need to point out whether the motilin-ghrelin receptor family will make it as a new class of gastroprokinetics.
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PMID:Motilin and ghrelin as prokinetic drug targets. 1942 31

Ghrelin increases hunger sensation and food intake in various patients with appetite loss. Anorexia nervosa (AN) begins with psychological stress-induced anorexia and some patients cannot increase their food intake partly because of malnutrition-induced gastrointestinal dysfunction. The effects of ghrelin on appetite, food intake and nutritional parameters in anorexia nervosa (AN) patients were examined. Five female restricting- type AN patients (age: 14-35 y; body mass index: 10.2-14.6 kg/m(2)) had persistently complained of gastrointestinal symptoms and failed to increase body weight. They were hospitalized for 26 days (6 days' pretreatment, 14 days' ghrelin-treatment, and 6 days' post-treatment) and received an intravenous infusion of 3 microg/kg ghrelin twice a day. Ghrelin infusion improved epigastric discomfort or constipation in 4 patients, whose hunger scores evaluated by visual analogue scale questionnaires also increased significantly after ghrelin infusion. Daily energy intake during ghrelin infusion increased by 12-36 % compared with the pre-treatment period. Serum levels of total protein and triglyceride as nutritional parameters significantly increased after ghrelin treatment. There were no serious adverse effects including psychological symptoms. We found that ghrelin decreases gastrointestinal symptoms and increases hunger sensation and daily energy intake without serious adverse events in AN patients. Although the present study had major limitations of the lack of a randomized, placebo-controlled group, non-blindness of the investigators and the small number of patients recruited, it would contribute to further investigations for therapeutic potential of ghrelin in AN patients.
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PMID:Ghrelin increases hunger and food intake in patients with restricting-type anorexia nervosa: a pilot study. 1975 53

The discovery of ghrelin has elucidated the role of the stomach as an important organ in the regulation of growth hormone release and energy homeostasis. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the blood stream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Ghrelin is a peptide hormone, in which serine 3 (threonine 3 in frogs) is modified by an n-octanoic acid; this modification is essential for ghrelin's activity. Recently the enzymes responsible for the processing from the ghrelin precursor to active n-octanoyl-modified ghrelin have been identified. This review surveys the processing pathway from ghrelin gene to mature ghrelin peptide and summarizes our knowledge of the regulatory mechanism of ghrelin secretion and function.
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PMID:Ghrelin: from gene to physiological function. 1985 76

Ghrelin is a peptide hormone released by the stomach that stimulates hunger. Ghrelin also suppresses reproductive physiology by inhibiting the HPG axis. However, to our knowledge, our results are the first to demonstrate ghrelin's quick suppression of sex-hormone-regulated behaviors. In experiment 1, 2 orexigenic i.p. ghrelin injections (0.165 mg/kg and 0.33 mg/kg) suppressed male courtship behavior (ultrasonic calling to a female) and intermale aggression (latency to attack a stimulus male) 20 min following administration. Experiment 2 (examining only the 0.33 mg/kg dose ) replicated ghrelin's suppression of ultrasonic calling and intermale aggression; however, a third behavior, preference for volatile female odors (20 min following administration), was not significantly inhibited. In experiment 2, ghrelin treatment did not affect general locomotor activity (distance traveled 20 min following injection) or seminal vesicle weight (measured 5 days after completing ghrelin injections). We hypothesize that ghrelin's quick suppression of male aggression and ultrasonic mating calls was mediated through its effects on the brain (rather than indirectly through inhibition of the HPG axis).
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PMID:Ghrelin's quick inhibition of androgen-dependent behaviors of male house mice (Mus musculus). 2004 99

Ghrelin and peptide YY (PYY) stimulate hunger and satiety, respectively. The physiology of these hormones during normal meal intake remains unclear. This study was designed to compare the responses of these two hormones to meal intake between lean and obese Hispanic adolescents. A total of 10 obese and 7 lean Hispanic youth, aged 11-14 years, consumed two mixed meals, one small and one large, during which plasma measurements of active and total ghrelin and total PYY were obtained. Obese subjects tended to consume more calories during the small meal than lean subjects, although this did not reach statistical significance. Intake of the small meal significantly suppressed active ghrelin and stimulated PYY levels in the lean subjects, and these changes were further accentuated by the large meals. In obese subjects, the suppression of active ghrelin and stimulation of PYY by caloric intake were blunted. Interestingly, a paradoxical stimulation of active ghrelin levels was noted during the small meals in both lean and obese subjects. This stimulation was not seen during the larger meals in lean subjects, but remained present in the obese subjects. Thus, meal-related changes in active ghrelin and PYY are blunted in obese as compared to lean Hispanic subjects. This blunting could contribute to the development or worsening of obesity.
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PMID:Obese adolescents show impaired meal responses of the appetite-regulating hormones ghrelin and PYY. 2009 39

There exists a substantial need to identify new neuropharmacological targets to treat alcohol-dependent individuals. Ghrelin represents a gut-brain peptide, initially discovered as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The existing literature clearly demonstrates that ghrelin affects appetite and food intake. Both animal and human studies provide evidence that ghrelin not only influences hunger but also has a role in the search for rewarding substances, such as alcohol. Animal studies provide evidence that ghrelin stimulates the reward system, acting on specific brain reward nodes, and that ghrelin signaling is required for stimulation of the reward system by alcohol. Human studies show that ethanol acutely affects ghrelin levels. Interestingly, human studies with alcohol-dependent individuals suggest that higher ghrelin levels are associated with higher self-reported measurements of alcohol craving. Altogether, these findings suggest that the ghrelin system plays a role in alcohol dependence. Ghrelin antagonists (i.e., GHS-R1a antagonists and/or inverse agonists) might affect alcohol-seeking behavior, thus having therapeutic potential in alcohol use disorders. Future laboratory and clinical studies testing this hypothesis are warranted.
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PMID:Role of the ghrelin system in alcoholism: Acting on the growth hormone secretagogue receptor to treat alcohol-related diseases. 2044 Apr 17

Ghrelin is a hormone produced mainly by P/D1 cells which line the fundus of the stomach and epsilon cells of the pancreas that stimulate hunger. Ghrelin exists in an endocrinologicaly inactive (des-acyl ghrelin) and active (n-octanoyl-modified ghrelin) forms. The serum- and glucocorticoid-inducible kinase 1 (SGK-1) is a member of the AGC family of serine/threonine protein kinase. In this study, mice were isolated individually or in groups, and deprived from food supply for a period of 24-h. Despite decreases in plasma corticosterone levels and no changes in plasma des-acyl ghrelin, and the expression of hypothalamic neuropeptide Y and proopiomelanocortin, plasma active ghrelin levels and the expression of hypothalamic SGK-1 were increased in the acute-isolated mice. Injection of SGK-1 small interfering RNA (siRNA) oligonucleotide into the third cerebral ventricle suppressed the acute social isolation-induced decreases in body weight and increases in plasma active ghrelin levels. Pretreatment with phentolamine (alpha-adrenergic receptor antagonist) but not alprenolol (beta-adrenergic receptor antagonist), partially but significantly suppressed the decreases in body weight induced by acute isolation stress. These finding suggest that isolation stress is a novel inducer of hypothalamic SGK-1 expression. SGK-1 might contribute to the isolation stress-induced body weight reductions and increases in plasma active ghrelin levels via, at least partly, altered central autonomic outflow in mice.
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PMID:Contribution of central SGK-1 to the acute phase responses of mice to social isolation. 2051 7


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