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Given the effects of ghrelin on energy metabolism and hunger, it is a prominent target for development of anti-obesity treatments. It has been reported that immunization of rats against ghrelin resulted in decreased weight gain and adiposity relative control rats, even though both groups consumed an equivalent amount of food. This intriguing experiment suggests the possibility of a vaccine against obesity.
Control of ghrelin secretion remains poorly understood. Other hormones that influence it's secretion include estrogen and leptin, but a comprehensive understanding of, for example, short term control of secretion from the stomach, is lacking. Ghrelin concentrations in blood are reduced in obese humans compared to lean control subjects, but whether this is cause or effect is not defined.
Patients with anorexia nervosa have higher than normal plasma ghrelin levels, which decrease if weight gain occurs. Additional studies might therefore still be valuable to further study the physiological involvement of ghrelin in GH release. Nevertheless, the potential beneficial effects of ghrelin analogs for the treatment of GH-deficiency disorders have been investigated [ ].
Desacyl ghrelin is also able to induce GH secretion, possibly by modulating the GH-insulin growth factor axis [ ]. Both central and peripheral administration of ghrelin to rats induces food intake stimulation and energy expenditure reduction accounting for body weight increase [ — ].
Ghrelin administrated intravenously to human also leads to appetite increase and food intake stimulation [ ]. Ghrelin is secreted in a pulsated manner as its level increases before the onset of meal, during fasting, and decreases after feeding [ , ].
This pulsatile secretion of ghrelin suggested that ghrelin may act as a signal for meal initiation. However, it appears that peaks of ghrelin concentrations are related to meal patterns and may rise in anticipation of eating rather than elicit feeding [ ].
Orexigenic and anorexigenic peptides control appetite. Among orexigenic peptides neuropeptides Y NPY , agouti-related peptide AGRP , orexins, melanin-concentrating hormone MCH , and galanin , ghrelin is the only one acting peripherally to stimulate appetite, while all other orexigenic peptides are acting centrally. Furthermore, in the hypothalamus, cannabinoids induce food intake via the cannabinoid receptor type 1 CB1 [ , ] Figure 6.
Ghrelin stimulates appetite by central and peripheral pathways and via the vagus nerve. Indeed, ghrelin is locally synthesized in the hypothalamus [ ], ghrelin secreted by the stomach reaches the brain by crossing the blood-brain barrier [ ], and ghrelin also transmits its signal through the vagal nerve [ ]. In hypothalamus, ghrelin activates the arcuate nucleus ARC , paraventricular nucleus PVN , dorsomedial region, central nucleus of amygdala, and the nucleus of solitary tract [ , ].
The activation of the hypothalamic AMPK signaling cascade results in an increase of appetite and food intake Figure 7. However, a recent study demonstrated that the effect of ghrelin on AMPK signaling pathway occurs independently from GHS-R1A, thereby suggesting that the AMPK signaling pathway does not play a major role in the orexigenic effect of ghrelin [ ].
SIRT1 is a deacetylase activated in response to calorie restriction that acts through the tumor suppressor p Hypothalamic mTOR signaling is involved in food intake [ , ]. It has been shown that hypothalamic mTOR signaling mediates the orexigenic action of ghrelin [ , , ].
These data appear to be opposed to those showing that activation of mTOR signaling promotes anorexia [ , ]. The intact cannabinoids signaling pathway is required for the effect of ghrelin on appetite and AMPK [ , , ]. Furthermore, control of AMPK signaling pathway by cannabinoids requires an intact ghrelin signaling pathway [ ].
Both in GHSR and ghrelin knockout mice, food intake is similar to littermate wild-type mice [ , ]. In light of the complexity of the hypothalamic ghrelin-signaling pathways, more studies are required to investigate more profoundly their relative importance in food intake and also investigate their possible activation in certain regions of the hypothalamus.
Furthermore, additional studies will be required to better understand the interactions between ghrelin and cannabinoids signaling and their implication in the control of food intake. Ghrelin also stimulates appetite via the vagus nerve. Human nodose ganglion from the vagus nerve expressing GHS-R1A are likely to be involved in the ghrelin-induced signal transmission from the stomach to the brain [ , ].
Indeed, rats submitted to vagotomy or perivagal application of an afferent neurotoxin [ ] or patients with vagotomy and esophageal or gastric surgery are responding to the appetite stimulatory effect of ghrelin [ , ]. Thus, through the activation of GHS-R on vagal afferent to the stomach, the signal induced by ghrelin may reach the nucleus of tractus solitarius, which communicates with the hypothalamus to increase food intake.
However, intraperitoneal injection of ghrelin stimulates eating in rats with subdiaphragmatic vagal deafferentation, suggesting that the ghrelin signal does not involve vagal afferents [ ]. The clinical applications of ghrelin have been investigated in both eating disorders and muscle wasting conditions, including obesity, anorexia nervosa, cachexia, and sarcopenia for a review see [ ].
Ghrelin is involved in long-term body weight regulation. Plasma ghrelin levels are negatively correlated with body weight in anorexia nervosa, cachexia, and obesity and fluctuate in a compensatory manner to body weight modifications [ 39 ]. Indeed, ghrelin levels decrease with weight gain resulting from different conditions such as overfeeding [ ], pregnancy [ ], olanzapine treatment [ ], or high fat diet [ ]. Conversely, ghrelin levels increase with weight loss resulting from conditions such as food restriction [ ], long-term chronic exercise but not acute exercise [ ], cachectic states induced by anorexia nervosa [ 39 ], severe congestive heart failure [ ], lung cancer [ ], and breast and colon cancers [ ].
Data on ghrelin levels after weight loss induced by gastric bypass surgery remain controversial as some studies found a decrease [ — ], no change [ — ] or an increase of ghrelin levels [ — ]. However variations in surgical procedures and patient treatment may account for the discrepancies.
In vivo , chronic ghrelin administration induces adiposity [ , ]. In addition to stimulate food intake, ghrelin reduces energy expenditure, consequently decreasing utilization and oxidation of fat while increasing utilization of carbohydrates [ ].
In vitro , ghrelin stimulates differentiation of preadipocytes [ ], adipogenesis [ ], inhibits adipocyte apoptosis [ ], and antagonizes lipolysis [ , ]. Furthermore, ghrelin shifts food preference towards high fat diets [ ]. GHSR and ghrelin knockout mice have been useful in determining the role of ghrelin in energy homeostasis. GHSR knockout mice, with C56Bl6J background, fed on normal diet displayed slight decrease in body weight, with no modification of food intake, as compared to wild-type mice [ ].
However, GHSR knockout mice, with C56Bl6Jsv background, fed on normal diet displayed normal body weight, but exhibited resistance to diet-induced obesity and lower fat mass when fed on high fat diet, compared to wild-type mice [ ]. These latter observations are likely to result from the effect of the genetic background as C56Bl6Jsv mice are inherently more resistant to diet-induced obesity compared to C56Bl6J knockout mice.
Ghrelin knockout mice displayed normal food intake, body weight, and body composition when compared to wild-type littermates [ , ]. Furthermore, ghrelin knockout mice presented intact hypothalamic regulatory feeding centers [ ]. Ghrelin knockout mice fed with high fat diet were resistant to diet-induced obesity [ , , ]. Very recently, it was shown that congenic adult ghrelin knockout mice submitted to either a positive high-fat diet or negative caloric restriction energy balance displayed similar body weight as wild-type littermates [ ].
However, interpretation of ghrelin knockout mice should be taken with caution as proghrelin yields several other peptides besides ghrelin that may play roles in the overall metabolism linked to ghrelin itself. Further studies are required to determine if ghrelin plays a role in the development of obesity. In patients with Prader-Willi syndrome PWS , a genetic disorder characterized by mental retardation and hyperphagia leading to severe obesity, plasma ghrelin levels are higher than in healthy subjects and do not decrease after a meal [ , ].
Other studies showed that ghrelin levels decreased postprandially in adult patients with PWS, but to a lesser extent than in obese and lean subjects [ , ].
This lesser postprandial ghrelin suppression may be due to a blunted postprandial response of PYY, an anorexigenic peptide that decreases postprandial ghrelin levels. Interestingly, children 5 years of age and younger with PWS have normal ghrelin levels.
Since these children have not yet developed hyperphagia or excessive obesity; it suggests that ghrelin levels increase with the onset of hyperphagia [ , ].
In opposition with these data, plasma ghrelin levels in children with PWS were elevated at any age, including the first years of life, thus preceding the development of obesity [ ]. Thus, ghrelin may be responsible, at least partially, for the insatiable appetite and the obesity of these patients.
These peripheral actions of ghrelin require p53 [ ] and cannabinoid receptor type 1 CB1 [ ]. Ghrelin, administrated peripherally, dose-dependently increases gastric acid secretion [ , ], by a mechanism involving the vagus nerve [ , ] and histamine synthesis and release [ ].
Furthermore, ghrelin acts in synergy with gastrin to stimulate gastric acid secretion [ , ]. Ghrelin, administrated centrally, either induces [ ] or inhibits [ , ] gastric acid secretion and possibly involves the vagus nerve. Furthermore, gastric acid secretion induced by ghrelin involves nitric oxide pathway [ , ].
In vitro , ghrelin dose-dependently enhances the after-contraction of gastric smooth muscle cells elicited during electrical field stimulation [ — ]. Furthermore, ghrelin acts on cholinergic and tachykinergic neurotransmission [ — ].
Ghrelin has no effect in vitro on the contractility of human and rodent colon muscle strips [ , — ]. In vivo , several studies have shown a dose-dependent effect of ghrelin on gastric emptying and intestinal transit following peripheral or central administration of ghrelin in rodents [ , , — ].
The vagus nerve is involved in the prokinetic action of ghrelin [ , , ]. Ghrelin also activates the migrating motor complex in rodent stomach and small intestine [ — ] by a mechanism involving the vagus nerve [ ]. However, a contradictory study showed no effect of ghrelin on the migrating motor complex in mice [ ]. In agreement with in vitro studies on colonic contractility [ , ], peripheral administration of ghrelin has no effect on colonic transit in rodents [ , ].
However, central administration of ghrelin stimulates colonic motility [ , ]. The poor capacity of ghrelin to cross the blood-brain barrier could account for the lack of peripheral administration of ghrelin on colonic motility. In humans, peripheral administration of ghrelin induces accelerated gastric emptying [ ] with no modification of orocecal and colonic transit [ ].
Besides, ghrelin stimulates the human migrating motor complex [ ]. Furthermore, ghrelin has been shown to have a series of important therapeutic potentials for the treatment of gastrointestinal motility disorders [ , ]. Therefore, future studies are needed to study the beneficial effects of novel ghrelin receptor agonists in gastrointestinal motility disorders. Numerous studies support a role for ghrelin in blood glucose homeostasis [ , , ].
Both the effects of ghrelin on insulin secretion and vice versa have been described. The inverse relationship between blood ghrelin levels and insulin levels has suggested the existence of an inhibitory feedback between ghrelin and insulin [ 8 , , ].
Ghrelin was first demonstrated to negatively affect insulin secretion in human [ ]. However, depending on experimental conditions, ghrelin either stimulates [ , ] or inhibits insulin secretion [ , ]. Indeed, ghrelin might have an inhibitory effect on insulin secretion at low concentrations and a stimulatory effect at high concentration [ ]. The mechanisms involved in the inhibitory effect of ghrelin on glucose-induced insulin secretion include an increase expression of the insulinoma-associated protein 2 IA-2 [ ] and the activation of the AMPK-uncoupling protein 2 UCP2 pathway [ , ].
Insulin decreases ghrelin levels independently of glucose concentrations [ , — ]. However, contradictory data showed no negative effect of insulin on ghrelin concentrations [ , ]. These discrepancies could be due to different experimental settings. Maintenance of glucose homeostasis includes the ability of the central nervous system to sense changes in glucose levels. Increased ghrelin levels during preprandial and fasting periods [ , , ] and hypothalamic GHSR expression [ ] suggest the involvement of a central mechanism whereby the ghrelin system can sense decreasing glucose concentrations [ ].
Besides, glucose responding neurons are also present in hypothalamic ventromedial nucleus, lateral hypothalamic area, and the parvocellular area of the paraventricular nucleus. These regions represent important targets for the orexigenic and energy homeostatic effects of ghrelin [ , ], and glucose sensing neurons respond to ghrelin [ ].
Moreover, GHSR is expressed adjacent to these hypothalamic regions [ , ]. Activation of neurons from the nucleus of solitary tract by insulin-induced hypoglycemia triggers an orexigenic response involving neurons containing ghrelin [ , ].
Future studies are warranted to determine how ghrelin leads to insulin counter-regulatory effects and central control of glucose homeostasis. Ghrelin stimulates liver glycogenolysis and neoglucogenesis and prevents suppression of glucose production by insulin, and thereby participate to increased blood glucose concentrations [ — ].
However, desacyl ghrelin dose-dependently inhibits liver glucose production [ ]. GOAT could be involved in glucose homeostasis as well.
Indeed GOAT knockout mice present improved glucose-induced insulin secretion and glucose tolerance [ 41 ]. Besides, GOAT knockout mice submitted to severe caloric restriction displayed severe hypoglycemia that can result into death [ 41 ].
However, those data have not been confirmed in another study using GOAT knockout mice submitted to caloric restriction [ ].
Distinct genetic background of the mouse strains uses and experimental conditions could account for these discrepancies. It remains to be proven, by future studies, if GOAT indeed plays a role in the control of glucose homeostasis.
In summary, the role of ghrelin and GOAT in the control of glucose homeostasis remains controversial and mechanistically poorly understood. However, due to the crucial role of glucose homeostasis, certainly further studies are required to address these issues.
Nevertheless, due to the possible involvement of ghrelin in the control of glucose homeostasis, ghrelin receptor already represents a therapeutic target for the treatment of type 1 and type 2 diabetes [ , ]. Ghrelin has been shown to have diverse cardiovascular functions [ — ]. Ghrelin decreases mean arterial pressure without altering the heart rate in healthy subjects [ ]. In animal models with heart failure, ghrelin improved cardiac output and contractility and attenuated left ventricular remodeling and development of cachexia [ ].
In patients with chronic heart failure, ghrelin improved left ventricular function, increased cardiac output and cardiac index, decreased systemic vascular resistance, and increased muscle strength [ ]. Ghrelin improved cardiac contractility and left ventricular function in chronic heart failure and reduced infarct size [ ].
The mechanisms responsible for the hypotensive effects of ghrelin include the suppression of sympathetic activity [ ] or direct vasodilatory action [ — ]. Ghrelin dilates human artery in an endothelium-independent manner [ , ]. In rats with myocardial infarction, chronic ghrelin treatment suppressed cardiac sympathetic activity and prevented early left ventricular remodeling [ ], while acute ghrelin treatment improved survival by preventing the increase of frequency of ventricular arrhythmias [ ].
Furthermore, the vasodilatory action of ghrelin involves activation of PI3 kinase, AKT, and endothelial nitric oxide synthase [ , ]. Interestingly, desacyl ghrelin is as potent as acyl ghrelin in exerting cardioprotective effects, probably by acting on an as yet unidentified receptor distinct from GHS-R1A [ ].
Besides, desacyl ghrelin improves vascular neovascularisation and, namely, in diabetic patients. Ghrelin is able to block the rennin-angiotensin system in humans and thereby improve hypertension and cardiovascular disorders as well as conditions associated with increased risk of developing cardiovascular disease such as disorders of glucose metabolism, dyslipidemia, and inflammatory states [ ].
Ghrelin plays multiple beneficial cardiovascular functions, thereby improving cardiovascular disease. Additional investigations are required for a thorough understanding of the detailed functions of ghrelin in the cardiovascular system in normal and pathological conditions. Surely, the usefulness of ghrelin analogs for the treatment of cardiovascular disease remains to be fully addressed and proven by adequate clinical studies.
Several studies have reported that ghrelin is able to exert anti-inflammatory actions by inhibiting the production of proinflammatory cytokines [ — ]. Indeed, ghrelin exerts anti-inflammatory actions in inflammatory bowel disease, pancreatitis, sepsis, arthritis, and diabetic nephropathy [ — ].
Despite limited clinical value, ghrelin administration prior to the development of experimental pancreatitis improved pancreatic blood flow, reduced IL1 levels, and stimulated pancreatic cell proliferation [ ]. In sepsis, ghrelin, via an upregulation of MAPK phosphatase 1, reduced norepinephrine and TNF levels known to cause hepatocellular dysfunction and upregulation of proinflammatory cytokines [ ].
Furthermore, organ blood flow is improved by ghrelin via an inhibition of NF-kB [ ] and HMGB1 production by activated macrophages is inhibited by ghrelin [ ]. Ghrelin reduced IL6 levels and symptoms of arthritis in an animal model [ ]. IL6 and IL8 levels induced by insoluble fibrillary -amyloid protein deposition in mouse microglia are decreased by desacyl ghrelin but not by acyl ghrelin probably by a mechanism involving, as already eluded to, an unidentified receptor distinct from GHS-R1A [ ].
Antihyperalgesic and anti-inflammatory effects of both acyl ghrelin and desacyl ghrelin have been shown in rats [ ]. Development of experimental diabetic nephropathy in mice can be prevented by acyl ghrelin acting on GHS-R1A [ ]. Further studies are definitively required to evaluate the potential benefit of ghrelin treatment for inflammatory-related conditions.
Ghrelin affects the hypothalamic-pituitary gonadal axis as well as female and male reproduction systems. Systemic actions of ghrelin on the hypothalamic-pituitary gonadal axis include inhibition of hypothalamic gonadotropin-releasing hormone GnRH and of both LH and FSH secretion [ — ] and stimulation of prolactin [ ].
Identification of the precise mechanisms accounting for the effects of ghrelin on the hypothalamic-pituitary gonadal axis will require further experimentation. In the female reproduction system, both ghrelin and GHS-R are present in ovary [ — ]. Depending on species, ghrelin exerts an inhibitory or stimulatory effect on steroidogenesis progesterone and estradiol production [ — ]. Ghrelin promotes proliferation and inhibits apoptosis of ovarian cells [ , ].
Both ghrelin and GHS-R have been detected in oocytes and different stages of embryo development [ ]. The effects of ghrelin on embryo development remain controversial [ , ]. Both ghrelin and GHS-R have been detected in placenta from several species [ , ]. Ghrelin stimulates the proliferation, inhibits the apoptosis, decreased progesterone secretion, and did not modify human chorionic gonadotropin hCG secretion of human placental JEG-3 cells [ ].
In the male reproduction system, both ghrelin and GHS-R are localized in testis, mainly in Leydig and Sertoli cells, but their localization varies depending on species [ — ]. Ghrelin regulates testicular stem cell factor and impairs Leydig cell proliferation [ ].
It has been suggested that elevated ghrelin levels could contribute to male reproductive alterations, especially in situations of energy deficiency [ ]. Further studies are required to gain insights into the understanding of the detailed mechanism of action of ghrelin in the female and male reproductive systems.
Bone formation is induced by ghrelin that stimulates osteoblastic cell proliferation and differentiation, inhibits cell apoptosis, and increases bone mineral density [ — ].
In several species, ghrelin stimulates osteoblast proliferation and differentiation but inhibits apoptosis [ , ]. The absence of GHS-R1A expression and the presence of GHS-R1b expression [ 13 , ] on osteoblasts suggest that ghrelin-mediated effects are mediated by an as yet unidentified mechanism.
The role of ghrelin on osteoclast function remains poorly understood as it has been shown to either enhance osteoclast resorption [ ] or inhibit osteoclast differentiation [ ]. Chronic central ghrelin administration increases rat bone mass through a mechanism independent of appetite regulation [ ].
Per os ghrelin administration induces new bone formation and stimulates intramembranous bone repair of calvarial bone defects in rats [ ]. In human, blood ghrelin level was positively correlated with bone mineral density in perimenopausal, postmenopausal, and premenopausal women, while it was significantly decreased in perimenopausal and postmenopausal women as compared to premenopausal women [ ].
In elderly women, but not in men, ghrelin levels were associated with trabecular bone mass density but not with total or cortical bone mass density [ ]. In obese adolescent girls, ghrelin is a negative predictor for bone mineral density and content [ ].
In a randomised, double-blind, placebo-controlled study, ghrelin infusion had no acute effect on markers of bone turnover in healthy controls and postgastrectomy subjects but was inversely correlated with bone resorption [ ]. Further studies are needed to precise the molecular mechanisms involved in ghrelin-mediated effects on the different bone cell types and on bone formation, and to investigate its potential use to treat elderly patients suffering from osteoporosis or at risk.
Ghrelin is peptide hormone that is essentially secreted by the stomach into the blood stream, but other tissues have been shown to also synthesize it. GHS-R1A receptor binds acyl ghrelin and is supposed to mediate its biological effects. However, it is recognized that both GHS-R1A homo- or heterodimers could be involved in the ghrelin-mediated actions. The formation of homo- and heterodimers is adding another level of complexity in the understanding of the actions of ghrelin.
Growing bodies of evidence support an increased number of functions for desacyl ghrelin. However the exact mechanisms and a potential specific receptor have thus far eluded determination. Much work remains to be done to determine if this additional level of complexity is indeed accounting for the biological effects of ghrelin.
Numerous and varied physiological effects of ghrelin, as reviewed in this paper, have been reported. However, it appears important to perform further studies to better understand the fine underlying mechanisms accounting for these pleiotropic ghrelin actions.
Furthermore, current understanding of ghrelin biology and biological functions has led to the development of pharmacological tools modulating ghrelin actions and the evaluation of their clinical applications. This work was supported by Grant 3. The author thanks Jason Perret for his help and comments in revising this paper. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. Special Issues. Academic Editor: E. Received 08 Oct Accepted 10 Nov Published 28 Nov Abstract Ghrelin is a gastric peptide hormone, discovered as being the endogenous ligand of growth hormone secretagogue receptor.
Introduction Ghrelin is a unique 28 amino acid peptide containing an n -octanoyl group on the serine in position 3 that was purified from rat stomach in [ 1 , 2 ]. Figure 1. From ghrelin gene to ghrelin peptide. Following the transcription of ghrelin gene containing 2 exons black boxes and 5 introns white boxes , mature ghrelin mRNA is processed into preproghrelin and finally into several peptides, namely, ghrelin and obestatin.
Figure 2. Sequence homologies between mammalian ghrelin. Highlighted boxes indicate amino acid homologies among ghrelin from mammalian species. Figure 3. The highlighted box indicates the minimal active N-terminal pentapeptide core of ghrelin sequence required for GHS-R1A activation.
Figure 4. Proposed controlled steps necessary to allow accurate ghrelin levels determination. Figure 5. Figure 6. Main hypothalamic pathways involved in ghrelin-induced food intake. Arrows and lines indicate stimulation and inhibition, respectively. Figure 7. Molecular mechanisms leading to ghrelin-induced food intake in the hypothalamus. References M. Kojima, H.
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Kanamoto, T. Akamizu, T. Nakai, M. Kaneko, N. Nakao et al. Seim, C. Collet, A. Herington, and L. Korbonits, A. Goldstone, M. Gueorguiev, and A. Pemberton, P. Wimalasena, T. Yandle, S. Ghrelin fluctuation, what determines its production? Xuefeng Yin , Xuefeng Yin. Oxford Academic. Yin Li. Geyang Xu. Wenjiao An. Select Format Select format. Permissions Icon Permissions. Abstract Ghrelin, a 28 amino acid gut brain peptide, acts as an endogenous ligand for its receptor, the growth hormone secretagogue receptor, to exercise a variety of functions ranging from stimulation of growth hormone secretion, regulation of appetite and energy metabolism, and cell protection to modulation of inflammation.
Open in new tab Download slide. Structure of human ghrelin gene and its processing. Table 1 Alterations of serum ghrelin level under different conditions. Elevated ghrelin level. Depressed ghrelin level. Nutrients Fatty acids a , amino acids a Glucose, fatty acids a Hormones Glucagon a , IGF-1, estrogen a Insulin, growth hormone, somatostatin, leptin a , estrogen a Autonomic nervous system Vagus nerve activation Sympathetic nerve activation Physiological status Fasting, lean, youth Feeding a , obesity, aging a Pathological status Prader—Willi syndrome, anorexia nervosa, cachexia Metabolic syndrome, diabetes mellitus.
Open in new tab. Google Scholar Crossref. Search ADS. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. Genomic structure and characterization of the 5'-flanking region of the human ghrelin gene. Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts.
Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone.
From the cover: ghrelin octanoylation mediated by an orphan lipid transferase. Impaired intestinal proglucagon processing in mice lacking prohormone convertase 1. Prohormone convertase 1 is necessary for the formation of cholecystokinin 8 in Rin5F and STC-1 cells. Developmental changes in the pattern of ghrelin's acyl modification and the levels of acyl-modified ghrelins in murine stomach.
Extent and direction of ghrelin transport across the blood—brain barrier is determined by its unique primary structure. Ghrelin acts in the central nervous system to stimulate gastric acid secretion. Oral glucose load inhibits circulating ghrelin levels to the same extent in normal and obese children. Different responses of circulating ghrelin, obestatin levels to fasting, re-feeding and different food compositions, and their local expressions in rats. Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration.
Acylated ghrelin secretion is acutely suppressed by oral glucose load or insulin-induced hypoglycemia independently of basal growth hormone secretion in humans. Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin. Endocrine effects of food intake: insulin, ghrelin, and leptin responses to a single bolus of essential amino acids in humans.
Endocrine responses to the oral ingestion of a physiological dose of essential amino acids in humans. Carob pulp preparation rich in insoluble dietary fibre and polyphenols increases plasma glucose and serum insulin responses in combination with a glucose load in humans. Effects of insulin, leptin, and glucagon on ghrelin secretion from isolated perfused rat stomach. Circulating ghrelin concentrations are lowered by intracerebroventricular insulin.
Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. Glucagon-like peptide 1 GLP-1 suppresses ghrelin levels in humans via increased insulin secretion. Not insulin but insulin sensitivity, leptin, and cortisol are major factors regulating serum acylated ghrelin level in healthy women.
Serum ghrelin levels are suppressed in hypopituitary patients following insulin-induced hypoglycaemia irrespective of GH status.
Glucagon receptor expression and glucagon stimulation of ghrelin secretion in rat stomach. Glucagon suppression of ghrelin secretion is exerted at hypothalamus—pituitary level. Effects of growth hormone GH on ghrelin, leptin, and adiponectin in GH-deficient patients. Growth hormone and somatostatin directly inhibit gastric ghrelin secretion. Evidence that growth hormone exerts a feedback effect on stomach ghrelin production and secretion. Effects of estrogen and recombinant human insulin-like growth factor-I on ghrelin secretion in severe undernutrition.
Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels. Serum acylated ghrelin, adiponectin and leptin levels in normal-weight and obese premenopausal women.
Differential association of basal and postprandial plasma ghrelin with leptin, insulin, and type 2 diabetes. Gastric leptin, but not estrogen and somatostatin, contributes to the elevation of ghrelin mRNA expression level in fasted rats.
Central leptin gene therapy blocks high-fat diet-induced weight gain, hyperleptinemia, and hyperinsulinemia—increase in serum ghrelin levels. Gastric estrogen directly induces ghrelin expression and production in the rat stomach.
A comparison of oral and transdermal short-term estrogen therapy in postmenopausal women with metabolic syndrome. Fertil Steril. Involvement of cholinergic neurons in the regulation of the ghrelin secretory response to feeding in sheep.
Vagotomy dissociates short- and long-term controls of circulating ghrelin. Predictors of postabsorptive ghrelin secretion after intake of different macronutrients.
Effect of two fasting periods of different duration on ghrelin response to a mixed meal. Effect of oral glucose on acylated and total ghrelin secretion in acromegalic patients. Google Scholar PubMed. Novel ghrelin assays provide evidence for independent regulation of ghrelin acylation and secretion in healthy young men. Simultaneous decrease of plasma obestatin and ghrelin levels after a high-carbohydrate breakfast in healthy women. Differential responses of circulating ghrelin to high-fat or high-carbohydrate meal in healthy women.
Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. Effects of high-fat feeding and fasting on ghrelin expression in the mouse stomach. Effect of high-fat meals and fatty acid saturation on postprandial levels of the hormones ghrelin and leptin in healthy men. Postprandial response of plasma ghrelin levels to various test meals in relation to food intake, plasma insulin, and glucose.
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