Minireview: ghrelin and the regulation of energy balance--a hypothalamic perspective.
- Authors
- Horvath, T L; Diano, S; Sotonyi, P; Heiman, M; Tschöp, M
- Year
- 2001
- Journal
- Endocrinology
- PMID
- 11564668
- DOI
- 10.1210/endo.142.10.8490
The recently discovered hormone, ghrelin, has been recognized as an important regulator of GH secretion and energy homeostasis. Orexigenic and adipogenic ghrelin is produced by the stomach, intestine, placenta, pituitary, and possibly in the hypothalamus. The concentration of circulating ghrelin, principally derived from the stomach, is influenced by acute and chronic changes in nutritional state. To date, most studies focused on the role of ghrelin in GH secretion or its function in complementing leptin action to prevent energy deficits. The potential significance of ghrelin in the etiology of obesity and cachexia as well as in the regulation of growth processes is the subject of ongoing discussions. A large quantity of information based on clinical trials and experimental studies with ghrelin and previously available synthetic ghrelin receptor agonists (GH secretagogues) must now be integrated with a rapidly increasing amount of data on the central regulation of metabolism and appetite. In this overview, we summarize recent findings and strategies on the integration of ghrelin into neuroendocrine networks that regulate energy homeostasis.
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| Direct effect of ghrelin on leptin production by cultured rat white adipocytes. | Giovambattista A et al. | — | 2006 | → |
| Distribution of ghrelin-immunoreactive neuronal networks in the human hypothalamus. | Menyhért J et al. | — | 2006 | → |
| Expression of ghrelin receptor mRNA in the rat and the mouse brain. | Zigman JM et al. | — | 2006 | → |
| Ghrelin acts on the dorsal vagal complex to stimulate pancreatic protein secretion. | Li Y et al. | — | 2006 | → |
| Ghrelin: a hormone regulating food intake and energy homeostasis. | Gil-Campos M et al. | — | 2006 | → |
| Ghrelin, an endogenous growth hormone secretagogue with diverse endocrine and nonendocrine effects. | Bhatti SF et al. | — | 2006 | → |
| Ghrelin controls hippocampal spine synapse density and memory performance. | Diano S et al. | — | 2006 | → |
| Ghrelin localization in rat and human thyroid and parathyroid glands and tumours. | Raghay K et al. | — | 2006 | → |
| Ghrelin stimulates locomotor activity and accumbal dopamine-overflow via central cholinergic systems in mice: implications for its involvement in brain reward. | Jerlhag E et al. | — | 2006 | → |
| Growth hormone expression and secretion in pig pituitary and median eminence slices are not influenced by the VGF protein. | Saleri R et al. | — | 2006 | → |
| Gut hormones ghrelin, PYY, and GLP-1 in the regulation of energy balance [corrected] and metabolism. | Perez-Tilve D et al. | — | 2006 | → |
| In search of an effective obesity treatment: a shot in the dark or a shot in the arm? | Zigman JM et al. | — | 2006 | → |
| Integration of metabolic stimuli in the hypothalamic arcuate nucleus. | van den Top M et al. | — | 2006 | → |
| Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system. | Budak E et al. | — | 2006 | → |
| Intraparaventricular neuropeptide Y and ghrelin induce learned behaviors that report food deprivation in rats. | Jewett DC et al. | — | 2006 | → |
| Lupin-enriched bread increases satiety and reduces energy intake acutely. | Lee YP et al. | — | 2006 | → |
| Mechanisms of the anorexia of aging in the Brown Norway rat. | Wolden-Hanson T | — | 2006 | → |
| Neuropeptide Y in normal eating and in genetic and dietary-induced obesity. | Beck B | — | 2006 | → |
| Neuropeptide Y mediates ghrelin-induced feeding in the goldfish, Carassius auratus. | Miura T et al. | — | 2006 | → |
| Obese subjects respond to the stimulatory effect of the ghrelin agonist growth hormone-releasing peptide-2 on food intake. | Laferrère B et al. | — | 2006 | → |
| Peripheral ghrelin participates in the glucostatic signaling mediated by the ventromedial and lateral hypothalamus neurons. | Solomon A et al. | — | 2006 | → |
| The effect of increased lipid intake on hormonal responses during aerobic exercise in endurance-trained men. | Christ ER et al. | — | 2006 | → |
| The orexigenic effect of peripheral ghrelin differs between rats of different age and with different baseline food intake, and it may in part be mediated by the area postrema. | Gilg S et al. | — | 2006 | → |
| Thoughts for food: brain mechanisms and peripheral energy balance. | Abizaid A et al. | — | 2006 | → |
| Altered hypothalamic-pituitary-ovarian axis function in young female athletes: implications and recommendations for management. | Stafford DE | — | 2005 | → |
| A novel growth hormone secretagogue-1a receptor antagonist that blocks ghrelin-induced growth hormone secretion but induces increased body weight gain. | Halem HA et al. | — | 2005 | → |
| Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake. | Bugarith K et al. | — | 2005 | → |
| Brain somatic cross-talk: ghrelin, leptin and ultimate challengers of obesity. | Popovic V et al. | — | 2005 | → |
| Comparative study of plasma ghrelin levels in women with polycystic ovary syndrome, in hyperandrogenic women and in normal controls. | Panidis D et al. | — | 2005 | → |
| Consuming fructose-sweetened beverages increases body adiposity in mice. | Jürgens H et al. | — | 2005 | → |
| Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. | Havel PJ | — | 2005 | → |
| Differential effects of methamphetamine on expression of neuropeptide Y mRNA in hypothalamus and on serum leptin and ghrelin concentrations in ad libitum-fed and schedule-fed rats. | Crowley WR et al. | — | 2005 | → |
| Early changes in insulin secretion and action induced by high-fat diet are related to a decreased sympathetic tone. | Cruciani-Guglielmacci C et al. | — | 2005 | → |
| Effects of ghrelin on hypothalamic glucose responding neurons in rats. | Chen X et al. | — | 2005 | → |
| Ghrelin directly regulates bone formation. | Fukushima N et al. | — | 2005 | → |
| Ghrelin, energy balance, and weight in infants: the chicken or the egg? | Philipps AF | — | 2005 | → |
| Ghrelin-induced food intake and growth hormone secretion are altered in melanocortin 3 and 4 receptor knockout mice. | Shaw AM et al. | — | 2005 | → |
| Ghrelin in human medullary thyroid carcinomas. | Morpurgo PS et al. | — | 2005 | → |
| Ghrelin levels are increased in alcoholism. | Kraus T et al. | — | 2005 | → |
| Ghrelin levels before and after reduction of overweight due to a low-fat high-carbohydrate diet in obese children and adolescents. | Reinehr T et al. | — | 2005 | → |
| Ghrelin: more than a natural GH secretagogue and/or an orexigenic factor. | Ghigo E et al. | — | 2005 | → |
| Ghrelin stimulates appetite, imagination of food, GH, ACTH, and cortisol, but does not affect leptin in normal controls. | Schmid DA et al. | — | 2005 | → |
| Ghrelin, the same peptide for different functions: player or bystander? | Lago F et al. | — | 2005 | → |
| Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men. | Laferrère B et al. | — | 2005 | → |
| Hormonal and metabolic defects in a prader-willi syndrome mouse model with neonatal failure to thrive. | Stefan M et al. | — | 2005 | → |
| Hormonal and metabolic responses to acute ghrelin administration in patients with bulimia nervosa. | Fassino S et al. | — | 2005 | → |
| Hypothalamic obesity in a patient with craniopharyngioma: dysregulation of neurohormonal control of energy balance. | Maniatis AK et al. | — | 2005 | → |
| Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. | Elmquist JK et al. | — | 2005 | → |
| Increased fasting plasma ghrelin levels during alcohol abstinence. | Kim DJ et al. | — | 2005 | → |
| Inhibitory effect of ghrelin on food intake is mediated by the corticotropin-releasing factor system in neonatal chicks. | Saito ES et al. | — | 2005 | → |
| Limits to sustained energy intake IX: a review of hypotheses. | Speakman JR et al. | — | 2005 | → |
| Menopausal status influences the relationship between serum ghrelin levels and fat mass in healthy women. | Iwamoto I et al. | — | 2005 | → |
| Nocturnal ghrelin levels--relationship to sleep EEG, the levels of growth hormone, ACTH and cortisol--and gender differences. | Schuessler P et al. | — | 2005 | → |
| No significant effect of acute moderate alcohol intake on leptin levels in healthy male volunteers. | Dammann G et al. | — | 2005 | → |
| Obesity and metabolic syndrome in circadian Clock mutant mice. | Turek FW et al. | — | 2005 | → |
| Obesity and the neuroendocrine control of energy homeostasis: the role of spontaneous locomotor activity. | Castañeda TR et al. | — | 2005 | → |
| Peptide S is a novel potent inhibitor of voluntary and fast-induced food intake in rats. | Beck B et al. | — | 2005 | → |
| Postprandial ghrelin release in anorectic patients before and after weight gain. | Otto B et al. | — | 2005 | → |
| Regulation of ghrelin secretion by somatostatin analogs in rats. | Silva AP et al. | — | 2005 | → |
| Relationships between fasting plasma ghrelin levels and metabolic parameters in children and adolescents. | Park HS et al. | — | 2005 | → |
| Spontaneous 24-h ghrelin secretion pattern in fasting subjects: maintenance of a meal-related pattern. | Natalucci G et al. | — | 2005 | → |
| Stimulation of appetite by ghrelin is regulated by leptin restraint: peripheral and central sites of action. | Kalra SP et al. | — | 2005 | → |
| The endogenous growth hormone secretagogue (ghrelin) is synthesized and secreted by chondrocytes. | Caminos JE et al. | — | 2005 | → |
| The interoceptive cue properties of ghrelin generalize to cues produced by food deprivation. | Davidson TL et al. | — | 2005 | → |
| The many faces of ghrelin: new perspectives for nutrition research? | Otto B et al. | — | 2005 | → |
| The negative association between total ghrelin levels, body mass and insulin secretion is lost in hypercortisolemic patients with Cushing's disease. | Giordano R et al. | — | 2005 | → |
| Variants in the ghrelin gene are associated with metabolic syndrome in the Old Order Amish. | Steinle NI et al. | — | 2005 | → |
| Adaptation of ghrelin levels to limit body weight gain in the obese Zucker rat. | Beck B et al. | — | 2004 | → |
| Anabolic neuropeptides. | Williams G et al. | — | 2004 | → |
| Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. | van der Lely AJ et al. | — | 2004 | → |
| Brain circuits regulating energy homeostasis. | Horvath TL et al. | — | 2004 | → |
| Characterization of the rhesus monkey ghrelin gene and factors influencing ghrelin gene expression and fasting plasma levels. | Angeloni SV et al. | — | 2004 | → |
| Circulating ghrelin levels in the newborn are positively associated with gestational age. | Bellone S et al. | — | 2004 | → |
| Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. | Teff KL et al. | — | 2004 | → |
| Effects of insulin, leptin, and glucagon on ghrelin secretion from isolated perfused rat stomach. | Kamegai J et al. | — | 2004 | → |
| Ghrelin acts at the nucleus of the solitary tract to decrease arterial pressure in rats. | Lin Y et al. | — | 2004 | → |
| Ghrelin: a link between eating disorders, obesity and reproduction. | Gottero C et al. | — | 2004 | → |
| Ghrelin and truncated ghrelin variant plasmid vectors administration into skeletal muscle augments long-term growth in rats. | Xie QF et al. | — | 2004 | → |
| Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ. | Inui A et al. | — | 2004 | → |
| Ghrelin expression in hyperplastic and neoplastic proliferations of the enterochromaffin-like (ECL) cells. | Srivastava A et al. | — | 2004 | → |
| Ghrelin, hypothalamus-pituitary-adrenal (HPA) axis and Cushing's syndrome. | Giordano R et al. | — | 2004 | → |
| Ghrelin in the gastroenteric tract of birds: immunoreactivity expression. | Neglia S et al. | — | 2004 | → |
| Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers. | Frieboes RM et al. | — | 2004 | → |
| Inhibition of adipogenesis by ghrelin. | Zhang W et al. | — | 2004 | → |
| Investigation of obesity candidate genes on porcine fat deposition quantitative trait loci regions. | Kim KS et al. | — | 2004 | → |
| Leptin signaling. | Ahima RS et al. | — | 2004 | → |
| Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity. | Miraglia del Giudice E et al. | — | 2004 | → |
| Morning preprandial plasma ghrelin and catecholamine concentrations in patients with phenylketonuria and normal controls: evidence for catecholamine-mediated ghrelin regulation. | Schulpis KH et al. | — | 2004 | → |
| Neuroendocrinology of nutritional infertility. | Wade GN et al. | — | 2004 | → |
| Neuropeptidergic characterization of the leptin receptor mutated obese Koletsky rat. | Keen Rhinehart E et al. | — | 2004 | → |
| Overlapping and interactive pathways regulating appetite and craving. | Kalra SP et al. | — | 2004 | → |
| [Physiopathological features and diagnostic utility of ghrelin protein in pediatrics]. | Soriano-Guillén L et al. | — | 2004 | → |
| Plasma ghrelin in obesity before and after weight loss after laparoscopical adjustable gastric banding. | Hanusch-Enserer U et al. | — | 2004 | → |
| Regulation of peptide YY levels by age, hormonal, and nutritional status. | Tovar SA et al. | — | 2004 | → |
| Relationship between ghrelin and energy expenditure in healthy young women. | St-Pierre DH et al. | — | 2004 | → |
| Sleep enhances nocturnal plasma ghrelin levels in healthy subjects. | Dzaja A et al. | — | 2004 | → |
| Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGFBP-5 concentrations during 30-day continuous subcutaneous infusion of GH-releasing peptide-2 in older men and women. | Bowers CY et al. | — | 2004 | → |
| The critical role of the melanocortin system in the control of energy balance. | Seeley RJ et al. | — | 2004 | → |
| Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. | Havel PJ | — | 2004 | → |
| Acetylcholine does not play a major role in mediating the endocrine responses to ghrelin, a natural ligand of the GH secretagogue receptor, in humans. | Broglio F et al. | — | 2003 | → |
| Agouti-related peptide, neuropeptide Y, and somatostatin-producing neurons are targets for ghrelin actions in the rat hypothalamus. | Seoane LM et al. | — | 2003 | → |
| Cellular distribution and regulation of ghrelin messenger ribonucleic acid in the rat pituitary gland. | Caminos JE et al. | — | 2003 | → |
| Common gene polymorphisms and nutrition: emerging links with pathogenesis of multifactorial chronic diseases (review). | Loktionov A | — | 2003 | → |
| Deletion of ghrelin impairs neither growth nor appetite. | Sun Y et al. | — | 2003 | → |
| Endocrine and non-endocrine actions of ghrelin. | Broglio F et al. | — | 2003 | → |
| Endocrine effects of food intake: insulin, ghrelin, and leptin responses to a single bolus of essential amino acids in humans. | Knerr I et al. | — | 2003 | → |
| Endogenous ghrelin is an orexigenic peptide acting in the arcuate nucleus in response to fasting. | Bagnasco M et al. | — | 2003 | → |
| Enhanced plasma ghrelin levels in rats with streptozotocin-induced diabetes. | Masaoka T et al. | — | 2003 | → |
| Epidemiology, implications and mechanisms underlying drug-induced weight gain in psychiatric patients. | Zimmermann U et al. | — | 2003 | → |
| Evidence that growth hormone exerts a feedback effect on stomach ghrelin production and secretion. | Qi X et al. | — | 2003 | → |
| Excitatory effects of motilin in the hippocampus on gastric motility in rats. | Guan Y et al. | — | 2003 | → |
| Filling the interstices: ghrelin neurons plug several holes in regulation of energy balance. | Dallman MF | — | 2003 | → |
| Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. | Simonneaux V et al. | — | 2003 | → |
| Ghrelin and body weight regulation in the obese Zucker rat in relation to feeding state and dark/light cycle. | Beck B et al. | — | 2003 | → |
| Ghrelin and growth hormone secretagogue receptor are expressed in the rat adrenal cortex: Evidence that ghrelin stimulates the growth, but not the secretory activity of adrenal cells. | Andreis PG et al. | — | 2003 | → |
| Ghrelin and the endocrine pancreas. | Broglio F et al. | — | 2003 | → |
| Ghrelin, a widespread hormone: insights into molecular and cellular regulation of its expression and mechanism of action. | Gualillo O et al. | — | 2003 | → |
| Ghrelin gene in cichlid fish is modulated by sex and development. | Parhar IS et al. | — | 2003 | → |
| Ghrelin in chronic liver disease. | Tacke F et al. | — | 2003 | → |
| Ghrelin inhibits the development of mouse preimplantation embryos in vitro. | Kawamura K et al. | — | 2003 | → |
| Ghrelin promotes slow-wave sleep in humans. | Weikel JC et al. | — | 2003 | → |
| High constitutive signaling of the ghrelin receptor--identification of a potent inverse agonist. | Holst B et al. | — | 2003 | → |
| Hypothalamic neuropeptide Y/Y1 receptor pathway activated by a reduction in circulating leptin, but not by an increase in circulating ghrelin, contributes to hyperphagia associated with triiodothyronine-induced thyrotoxicosis. | Ishii S et al. | — | 2003 | → |
| Insulin-dependent modulation of plasma ghrelin and leptin concentrations is less pronounced in type 2 diabetic patients. | Anderwald C et al. | — | 2003 | → |
| Insulin is required for prandial ghrelin suppression in humans. | Murdolo G et al. | — | 2003 | → |
| Intraperitoneal injection of ghrelin induces Fos expression in the paraventricular nucleus of the hypothalamus in rats. | Rüter J et al. | — | 2003 | → |
| Involvement of novel feeding-related peptides in neuroendocrine response to stress. | Ueta Y et al. | — | 2003 | → |
| Leptin expression in hypothalamic PVN reverses dietary obesity and hyperinsulinemia but stimulates ghrelin. | Bagnasco M et al. | — | 2003 | → |
| Minireview: From anorexia to obesity--the yin and yang of body weight control. | Zigman JM et al. | — | 2003 | → |
| Natural and synthetic growth hormone secretagogues: do they have therapeutic potential? | Broglio F et al. | — | 2003 | → |
| Neural regulation of blood pressure by leptin and the related peptides. | Matsumura K et al. | — | 2003 | → |
| Neuropeptide Y: a physiological orexigen modulated by the feedback action of ghrelin and leptin. | Kalra SP et al. | — | 2003 | → |
| Non-acylated ghrelin does not possess the pituitaric and pancreatic endocrine activity of acylated ghrelin in humans. | Broglio F et al. | — | 2003 | → |
| Nutritional status in the neuroendocrine control of growth hormone secretion: the model of anorexia nervosa. | Scacchi M et al. | — | 2003 | → |
| Ontogeny of the hypothalamic neuropeptide Y system. | Grove KL et al. | — | 2003 | → |
| Post-prandial decrease of human plasma ghrelin in the absence of insulin. | Spranger J et al. | — | 2003 | → |
| Rhythmic, reciprocal ghrelin and leptin signaling: new insight in the development of obesity. | Kalra SP et al. | — | 2003 | → |
| Sleep and endocrinology. | Steiger A | — | 2003 | → |
| The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. | Cowley MA et al. | — | 2003 | → |
| The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. | Parent AS et al. | — | 2003 | → |
| Total and active ghrelin in developing rats during hypoxia. | Raff H | — | 2003 | → |
| Unopposed orexic pathways in the developing fetus. | Ross MG et al. | — | 2003 | → |
| Upregulation of cardiac ghrelin mRNA in leptin-deficient and leptin receptor-deficient mice with viral myocarditis. | Kanda T et al. | — | 2003 | → |
| Central ghrelin modulates sympathetic activity in conscious rabbits. | Matsumura K et al. | — | 2002 | → |
| Central leptin gene therapy blocks high-fat diet-induced weight gain, hyperleptinemia, and hyperinsulinemia: increase in serum ghrelin levels. | Dube MG et al. | — | 2002 | → |
| Delayed short-term secretory regulation of ghrelin in obese animals: evidenced by a specific RIA for the active form of ghrelin. | Ariyasu H et al. | — | 2002 | → |
| Discovery and optimization of a series of carbazole ureas as NPY5 antagonists for the treatment of obesity. | Block MH et al. | — | 2002 | → |
| Does body mass play a role in the regulation of food intake? | Speakman JR et al. | — | 2002 | → |
| Effect of food restriction on ghrelin in normal-cycling female rats and in pregnancy. | Gualillo O et al. | — | 2002 | → |
| Enhanced animal growth via ligand-regulated GHRH myogenic-injectable vectors. | Draghia-Akli R et al. | — | 2002 | → |
| Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. | Banks WA et al. | — | 2002 | → |
| Ghrelin and synthetic GH secretagogues. | Arvat E et al. | — | 2002 | → |
| Ghrelin and the hyposomatotropism of obesity. | Lindeman JH et al. | — | 2002 | → |
| Ghrelin is not necessary for adequate hormonal counterregulation of insulin-induced hypoglycemia. | Lucidi P et al. | — | 2002 | → |
| Ghrelin, macronutrient intake and dietary preferences in long-evans rats. | Beck B et al. | — | 2002 | → |
| Hypophysectomy prevents ghrelin-induced adiposity and increases gastric ghrelin secretion in rats. | Tschöp M et al. | — | 2002 | → |
| Insulin, unlike food intake, does not suppress ghrelin in human subjects. | Caixás A et al. | — | 2002 | → |
| Long-term suppression of weight gain, adiposity, and serum insulin by central leptin gene therapy in prepubertal rats: effects on serum ghrelin and appetite-regulating genes. | Beretta E et al. | — | 2002 | → |
| Multiple neural systems controlling food intake and body weight. | Berthoud HR | — | 2002 | → |
| Neuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity. | Muccioli G et al. | — | 2002 | → |
| Neuropeptides, food intake and body weight regulation: a hypothalamic focus. | Hillebrand JJ et al. | — | 2002 | → |
| Role of ghrelin polymorphisms in obesity based on three different studies. | Ukkola O et al. | — | 2002 | → |
| Selective antagonism of the NPY Y5 receptor does not have a major effect on feeding in rats. | Turnbull AV et al. | — | 2002 | → |
| The GH-releasing effect of ghrelin, a natural GH secretagogue, is only blunted by the infusion of exogenous somatostatin in humans. | Di Vito L et al. | — | 2002 | → |
| The need to feed: homeostatic and hedonic control of eating. | Saper CB et al. | — | 2002 | → |
| Weight in the balance. | Altman J | — | 2002 | → |