Role Of Ghrelin Research Articles

Role of ghrelin in the regulation of energy balance in adult male albino rats

Background Ghrelin is a 28-amino acid acylated peptide that was recently identified as endogenous ligand for growth hormone secretagogue receptor. It is a potent orexigenic peptide that stimulates food intake, adipogenesis, and body weight gain. However, its physiological role in the regulation of energy homeostasis is still controversial. Aim The study was performed to show the physiological role of ghrelin in energy balance and body weight homeostasis through assessing the effect of obesity and undernutrition on the plasma ghrelin level. Materials and methods Twenty-four adult male albino rats weighing 140–190 g were divided into three groups: group I (control group): rats of this group were given free access to food and water, group II (induction of obesity): rats of this group were fed a high-caloric diet for induction of obesity, and group III (chronic food restriction): rats of this group were fed by 30% of the diet consumed by the control group. Results The body weight is significantly increased in rats, which fed a high-caloric diet for induction of obesity, whereas plasma ghrelin level was significantly decreased. Food-restricted rats showed significantly decreased body weight and significantly elevated plasma ghrelin level. Conclusion These findings suggest that ghrelin has a pivotal role in mediating the physiological responses to undernutrition and overnutrition. Changes in the circulating level of ghrelin can represent an adaptative response to prevent long-lasting alterations in the energy balance and body weight.

A possible role for ghrelin, leptin, brain-derived neurotrophic factor and docosahexaenoic acid in reducing the quality of life of coeliac disease patients following a gluten-free diet.

A gluten-free diet (GFD) has been reported to negatively impact the quality of life (QoL) of coeliac disease (CD) patients. The gut-brain axis hormones ghrelin and leptin, with the brain-derived neurotrophic factor (BDNF), may affect QoL of CD patients undergoing GFD. Our aims were to evaluate whether: (a) the circulating concentrations of leptin, ghrelin and BDNF in CD patients were different from those in healthy subjects; (b) GFD might induce changes in their levels; (c) BDNF Val66Met polymorphism variability might affect BDNF levels; and (d) serum BDNF levels were related to dietary docosahexaenoic acid (DHA) as a neurotrophin modulator. Nineteen adult coeliac patients and 21 healthy controls were included. A QoL questionnaire was administered, and serum concentrations of ghrelin, leptin, BDNF and red blood cell membrane DHA levels were determined at the enrolment and after 1year of GFD. BDNF Val66Met polymorphism was analysed. Results from the questionnaire indicated a decline in QoL after GFD. Ghrelin and leptin levels were not significantly different between groups. BDNF levels were significantly (p=0.0213) lower in patients after GFD (22.0±2.4ng/ml) compared to controls (31.2±2.2ng/ml) and patients at diagnosis (25.0±2.5ng/ml). BDNF levels correlated with DHA levels (p=0.008, r=0.341) and the questionnaire total score (p=0.041, r=0.334). Ghrelin and leptin seem to not be associated with changes in QoL of patients undergoing dietetic treatment. In contrast, a link between BDNF reduction and the vulnerability of CD patients to psychological distress could be proposed, with DHA representing a possible intermediate.

Contents of ACTH and CRF in the rat blood serum after administration of orexin A antagonists in experimental alcoholization

In recent years, the role of ghrelin and orexin systems in the formation of alcoholic addiction has been demonstrated. The aim of the present investigation was to compare quantitatively the CRF and ACTH blood concentrations in the forced and chronic models of alcoholization, as well as the assessment of pharmacological action of synthetic and recombinant antagonists of orexin A on the system CRF-ACTH after experimental alcohol abuse. 89 adult male Wistar rats weighing 250-300 g Wistar were used in the experiment. All experimental animals were divided into 10 groups: intact, with chronic and forced alcoholization, with intranasal administration of orexin A antagonists on alcoholization process and agter its withdrawal. The chronic (during 6 months) and forced (5 days by means of elevating doses up to maximal ones) alcoholization slightly increased ACTH and CRF levels in the blood serum. The withdrawal of ethanol decreased the hormones level. Intranasal administration of orexin A antagonists (both synthetic and recombinant) slightly decreased the ACTH and CRF concentrations in the blood, in more degree after the forced alcoholization. In general, the systemic action of orexin A antagonists on the central stress mechanisms were expressed in little degree. The significant disorders in the ACTH-CRF system were not registered also, both after different regimens of alcoholizations and after intranasal administrations of orexin A antagonists.

D-Lys 3]-GHRP-6, an antagonist of ghrelin receptors, decreases expression of conditioned place preference reaction of ethanol in rats

Ghrelin is a peptide hormone synthesized and secreted by the stomach into the bloodstream. The greatest attention of neuroscience research is devoted to investigation of acylated form of ghrelin, which is a specific ligand for the receptor subcortical nuclei of the brain. The aim of this study was to analyze the action of ghrelin and its antagonist on the expression of conditioned place preference (СPP) of ethanol. To develop CPP of alcohol we used a two-chamber apparatus. Rats were spent 74 % of time experiment in chamber associated with alcohol. Rats receiving intranasal receptor ghrelin antagonist [D-Lys3]-GHRP-6 (10 µg) reduced the time of staying in the chamber associated with alcohol for 46 % (p < 0.05). Rats treated with intranasal ghrelin spent in the chamber, associated with alcohol, for 60 % of time. Then the extinction of CPP was produced when rats was replaced into the apparatus every day for 7 days without administration alcohol or any substances. On the 7th day of extinction, CPP was not reproduced. But after administration of ethanol on the 7th day CPP was reinstated. Animals received GHS-R1A receptor ghrelin antagonist [D-Lys3]-GHRP-6 (10 µg) and ethanol spent 50 % of time in chamber associated with the administration of ethanol, i.e. CPP was not reinstated. Animals treated with ghrelin, demonstrated a range of reactions from a sharp preference to avoidance of the place associated with ethanol. Thus, the present study shows the important role of ghrelin in the mechanisms of the reinforcing effects of alcohol and demonstrates the prospect for using of ghrelin antagonists in the correction of pathological craving in addictive disordes.

Appetite-related peptides in childhood and adolescence: role of ghrelin, PYY, and GLP-1.

During childhood and adolescence, a number of factors, including age, puberty, sex, race, and body composition, may contribute to differences in satiety, food intake, and appetite-related peptides. These peptides include the orexigenic peptide ghrelin and anorexigenic gut peptides peptide YY (PYY) and glucagon-like peptide-1 (GLP-1). For example, lower fasting ghrelin levels, lower postprandial ghrelin suppression, and blunted PYY and GLP-1 responses to food intake could contribute to a dysregulation of appetite in already obese children and adolescents. Whereas, changes in these peptides observed during puberty could facilitate growth. A greater understanding of the major moderating factors of appetite-related peptides in the pediatric population is essential to improve interpretation of study findings and for effective tailoring of strategies targeting appetite control to individuals. While more studies are needed, there is some evidence to suggest that exercise-based lifestyle interventions could be a potential therapeutic strategy to improve appetite-peptide profiles in overweight and obese children and adolescents. The aim of this review is (i) to discuss the potential moderating factors of ghrelin, PYY, and GLP-1, including age and puberty, sex, race and body composition; and (ii) to examine the effects of exercise interventions on these appetite-related gut peptides in children and adolescents.

Ghrelin and atherosclerosis.

The increasing prevalence of metabolic syndrome and the consequent cardiovascular diseases has stimulated an active search for novel risk factors. The hormones regulating energy balance are of special interest as potential risk factor indicators of cardiovascular diseases. Ghrelin provides an attractive target for studies of atherosclerosis being a gastric peptide hormone having multiple functions including orexigenic and growth hormone-releasing effects and is also involved in the regulation of cardiovascular and immunomodulatory system. The aim of the present article is to review recent studies on the role of ghrelin in the atherosclerosis. Ghrelin seems to influence known risk factors of atherosclerosis, endothelial dysfunction, inflammation and oxidation. These themes will be covered by the present article and a summary of clinical studies of ghrelin in atherosclerosis will be given. Ghrelin plays a beneficial role in multiple processes of atherogenesis and vascular function. However, ghrelin's effects are not as strong as those of traditional known risk factors.

Abstract 150: Association Between Serum Ghrelin Levels and Coronary Artery Disease: a Meta-analysis

Background: Ghrelin (GH) is a gastrointestinal endocrine peptide regulating multiple biological processes including adipogenesis, glucose metabolism, cell differentiation and proliferation. Recent studies demonstrated that GH inhibits pro-atherogenic changes in vessel wall via inhibition of nuclear factor - B activity, a transcriptional factor mediating production pro-inflammatory cytokines and adhesion molecule expression in the endothelium. The aim of the current study is to conduct a meta-analysis to evaluate the relationship between serum GH levels and coronary artery disease (CAD). Methods: We searched MEDLINE, CINHAL and COCHRANE databases for studies reporting serum GH levels in the CAD and non CAD study population. We included case controls, cohort and cross-sectional studies. We calculated the weighted standardized mean difference (SMD) in serum GH levels between the CAD and control groups. Results: Our search strategy yielded 285 articles and we included 10 studies enrolling 1855 participants. The median age of the CAD group was 62 yrs. (IQR 60 - 63) compared to 61 yrs. (IQR 58 - 65) in the control group. The median body mass index in the CAD group was 28 kg/m2 (IQR 27.9 - 28) compared to 27 kg/m2 (IQR 26 - 27) in the control group. The unweighted median serum GH levels in the CAD group were 0.66 ng/ml (IQR 0.3 - 1.6) compared to 0.76 ng/ml (IQR 0.38 - 4.9) in the control group. The SMD of GH level was -0.44 (95% CI -0.56,-0.31) p<0.001 comparing those in the CAD group and control group. Conclusion: Serum GH levels are significantly and inversely associated with CAD. Current findings warrant the need to further investigate the role of GH in the pathogenesis of CAD.

Chronic administration of ghrelin regulates plasma glucose and normalizes insulin levels following fasting hyperglycemia and hyperinsulinemia

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor. The majority of the previous studies have shown that the short-term ghrelin treatment induces hyperglycemia and hypoinsulinemia in healthy humans and rodents. However, the results obtained from long-term treatment with ghrelin are not clear enough. In this study, we assessed acute (1day) and chronic (21days) effects of intraperitoneally administered ghrelin (at different doses of 1, 10 and 20μg/kg) during a 12-h fasting period in rats using glucose oxidase method and direct sandwich ELISA (the Enzyme-Linked Immunosorbent Assay) and then compared the effects of exogenous ghrelin on blood glucose and insulin levels on day 21 with those on day 1. The results showed that acute ghrelin administration markedly increased fasting plasma glucose at doses of 1 and 10μg/kg as well as insulin levels at 1μg/kg in comparison to control values. Ghrelin (at 1μg/kg) altered plasma glucose but not insulin levels on the 21st day compared to control values. In addition, the comparison of the influence of ghrelin administration on plasma glucose and insulin levels on day 21 with those on the first day revealed that the chronic administration of ghrelin notably decreased plasma glucose and insulin levels relative to the acute ghrelin treatment. These findings indicate that hyperglycemia and hyperinsulinemia caused by the exogenous ghrelin during acute treatment are temporary and prolonged treatment with ghrelin regulates plasma glucose and restores insulin to normal levels, suggesting a possible role for ghrelin in improving insulin resistance.

AAV-mediated in vivo functional selection of tissue-protective factors against ischaemia.

Functional screening of expression libraries in vivo would offer the possibility of identifying novel biotherapeutics without a priori knowledge of their biochemical function. Here we describe a procedure for the functional selection of tissue-protective factors based on the in vivo delivery of arrayed cDNA libraries from the mouse secretome using adeno-associated virus (AAV) vectors. Application of this technique, which we call FunSel, in the context of acute ischaemia, revealed that the peptide ghrelin protects skeletal muscle and heart from ischaemic damage. When delivered to the heart using an AAV9 vector, ghrelin markedly reduces infarct size and preserves cardiac function over time. This protective activity associates with the capacity of ghrelin to sustain autophagy and remove dysfunctional mitochondria after myocardial infarction. Our findings describe an innovative tool to identify biological therapeutics and reveal a novel role of ghrelin as an inducer of myoprotective autophagy.

Plasma ghrelin and liquid gastric emptying in children with functional dyspepsia consistent with post-prandial distress syndrome.

Adult studies indicate a role for ghrelin in functional dyspepsia (FD) mediated through ghrelin's effect on gastric emptying (GE). This study examines the relationship between ghrelin, liquid GE, and pain in children with FD. Thirteen FD patients reporting symptoms consistent with post-prandial distress syndrome (PDS) and 17 healthy controls were enrolled. All participants received a liquid meal containing (13) C-sodium acetate. Pain severity, liquid GE utilizing exhaled (13) CO2 from the sodium acetate breath tests (ABT), plasma acyl ghrelin (AG), and des-acyl ghrelin concentrations were measured at specific intervals over 240 min following ingestion. FD-PDS patients demonstrated lower mean baseline AG (14.8 ± 9.7 vs 27.2 ± 14.0 fmol/mL; p = 0.013), AG Cmax (24.6 ± 8.2 vs 40.5 ± 16.8 fmol/mL; p = 0.007), and AG flux (18.2 ± 7.8 vs 32.7 ± 17.3 fmol/mL; p = 0.015) than controls. The time to reach maximum exhaled (13) CO2 concentration (T max ) was longer in FD patients than controls (47.5 ± 18.5 vs 35.8 ± 11.8 min; p = 0.046). Significant relationships between ghrelin analyte ratios and ABT parameters were largely confined to control participants. FD-PDS in children is associated with lower fasting and maximum AG concentrations, and dampened AG flux. These data suggest a possible role for altered ghrelin physiology in the pathogenesis of PDS.

Associations between Bone Mineral Characteristics and Serum Levels of Ghrelin and Peptide YY in Overweight Adolescent Boys

Background/Aims: The role of ghrelin and peptide YY (PYY) in bone mineralization is not fully known. The aim of this study was to determine whether acylated and des-acyl ghrelin and PYY in addition to leptin are related to bone mineral density (BMD) in adolescent overweight boys (OWB) and normal-weight boys (NWB). Participants and Methods: Fifty- five OWB (BMI >85th percentile) and 154 NWB (BMI <85th percentile) aged 12-16 years participated in this study. Fasting serum acylated and des-acyl ghrelin, PYY, leptin, testosterone levels, total body (TB) and lumbar spine (LS) bone mineral content (BMC), and BMD were measured. TB BMC for height and TB and LS bone mineral apparent density (BMAD) were calculated. Results: No differences were seen in acylated and des-acyl ghrelin or PYY levels, while the leptin levels were significantly higher in the OWB compared to the NWB. In the OWB, TB BMAD was positively correlated with acylated ghrelin and leptin, and TB BMC for height was positively correlated with PYY. In the OWB, the variability of TB BMD was determined by TB fat-free mass and des-acyl ghrelin, whereas the variability of TB BMAD was determined by leptin. Conclusions: Des-acyl ghrelin and PYY are involved in the bone mineralization process in puberty, and the impact can vary between normal and overweight subjects.

The role of ghrelin on apoptosis, cell proliferation and oxidant-antioxidant system in the liver of neonatal diabetic rats.

Ghrelin is a multifunctional peptide hormone which stimulates appetite and regulates glucose metabolism and adipogenesis. The purpose of this study was to investigate whether ghrelin has protective effects in the liver of streptozocin (STZ) diabetic rats or not. Wistar-type neonatal rats were divided into four groups: I. Controls, II. Ghrelin administrated controls, III. STZ-diabetic rats, and IV. Ghrelin administrated diabetic rats. On the second day after birth, 100 mg/kg STZ was administered intraperitoneally in a single dose to induce diabetes in rats. 100 µg/kg/day ghrelin was administrated to rats subcutaneously for 4 weeks. Ghrelin administration improved histopathologic changes in STZ-diabetic liver. Obestatin immunoreactivity has been shown in livers of neonatal rats. The immunoreactivity of obestatin increased in diabetic rats and a decline was observed in ghrelin administrated diabetic rats. Caspase 8 and 3 immunoreactivities increased in diabetic rats; however, ghrelin administration differently affected caspases 8 and 3 immunoreactivities. Proliferating cell nuclear antigen immunoreactivities decreased in diabetic rats and in ghrelin administrated diabetic rats. Serum alanine (P < 0.05) and aspartate transaminase (P < 0.0001) and serum alkaline phosphatase (P < 0.0001) activities were decreased in ghrelin administrated diabetic rats compared to the diabetic rats. Gamma glutamyl transferase activity (P < 0.001) decreased in ghrelin administrated diabetic rats compared to the diabetic rats. The response of antioxidants including glutathione levels, catalase and superoxide dismutase activities were altered in ghrelin administrated diabetic rats. Our findings indicate that ghrelin administration affects hepatic functions in neonatal diabetic rats and might be considered as a therapeutic agent.

Ghrelin and obestatin in thyroid gland - immunohistochemical expression in nodular goiter, papillary and medullary cancer.

Previous studies analyzing ghrelin and obestatin expression in thyroid gland tissue are not unanimous and are mostly related to ghrelin. The role of ghrelin and obestatin in the thyroid gland appears very interesting due to their probable involvement in cell proliferation. Furthermore, since the thyroid gland is associated with the maintenance of energy balance, the relationship between ghrelin, obestatin and thyroid function is worthy of consideration. The aim of the study was to assess ghrelin and obestatin immunocytochemical expression in nodular goiter (NG), papillary cancer (PTC) and medullary cancer (MTC). Analyzed samples included 9 cases of NG, 8 cases of PTC and 11 cases of MTC. The analysis of ghrelin and obestatin expression was performed by use of the immunohistochemical (IHC) EnVision system and evaluated with filter HSV software (quantitative morphometric analysis). Quantitative ghrelin expression in MTC cells was higher than in NG (p = 0.013) and correlated negatively with the size of the tumor (r= -0.829, p < 0.05). We did not observe any differences in ghrelin expression neither between MTC and PTC nor between NG and PTC. Obestatin immunoexpression pattern in all analyzed specimens was irregular and poorly accented. The strongest immunoreactivity for obestatin was demonstrated in NG. In MTC obestatin expression was significantly weaker than in NG and PTC (p < 0.05 in both cases). In NG the intensity of obestatin immunostaining was significantly higher than that of ghrelin (p = 0.03). Conversely, ghrelin expression in MTC was definitely more evident than obestatin immunoreactivity (p < 0.01). There was no statistically significant difference between ghrelin and obestatin expression in PTC. No correlations were detected between reciprocal tissue expressions of ghrelin and obestatin in the analyzed specimens of NG, PTC or MTC. The differences between ghrelin expression in NG and MTC suggest that ghrelin may be involved in thyroid cell proliferation. The differences between ghrelin and obestatin immunoreactivity in benign and malignant thyroid tumors could support the theory of alternative transcription of the preproghrelin gene and independent production of ghrelin and obestatin.

Expression and Clinical Significance of Ghrelin in Endometrial Hyperplasia and Carcinoma of Egyptian Patients

Endometrial carcinoma ranks the seventh most common malignant tumor worldwide. The distinction between atypical endometrial hyperplasia (AEH) and endometrial carcinoma, especially the well-differentiated grade, is particularly difficult with overlapping distinguishing criteria and small biopsy. Ghrelin is 28 amino acid peptide that is synthesized by gastric mucosa and is expressed in a variety of normal and tumor tissues. In endometrial tissue, it is expressed during the menstrual cycle, involved in the uterine development and cyclic growth. Data regarding role of Ghrelin in endometrial carcinoma are contradictory. In the present study, immunohistochemical expression of Ghrelin was evaluated in 55 endometrioid carcinoma cases, as well as 26 endometrial hyperplasia cases. The relationship between Ghrelin expression and clinicopathologic features of endometrioid carcinoma was studied as well. Ghrelin loss or reduced expression was significantly related to endometrioid carcinoma, especially the well-differentiated type, compared with AEH and EIN (p = 0.000 and 0.006, respectively). Ghrelin loss was also related to poorly differentiated histologic grades of endometrioid carcinoma (p = 0.04). Ghrelin loss is helpful in differentiation between AEH and EIN from endometrioid adenocarcinoma, especially the well-differentiated grade. It could be also related to poor differentiation.

Ghrelin Increases Beta-Catenin Level through Protein Kinase A Activation and Regulates OPG Expression in Rat Primary Osteoblasts.

Ghrelin, by binding growth hormone secretagogue receptor (GHS-R), promotes osteoblast proliferation but the signaling mechanism of GHS-R on these cells remains unclear. Since canonical Wnt/β-catenin pathway is critically associated with bone homeostasis, we investigated its involvement in mediating ghrelin effects in osteoblasts and in osteoblast-osteoclast cross talk. Ghrelin (10−10M) significantly increased β-catenin levels in rat osteoblasts (rOB). This stimulatory action on β-catenin involves a specific interaction with GHS-R1a, as it is prevented by the selective GHS-R1a antagonist, D-Lys3-GHRP-6 (10−7M). The effect of ghrelin on β-catenin involves the phosphorylation and inactivation of GSK-3β via protein kinase A (PKA). Inhibition of PKA activity reduces the facilitatory action of ghrelin on β-catenin stabilization. Ghrelin treatment of rOB significantly increases the expression of osteoprotegerin (OPG), which plays an important role in the regulation of osteoclastogenesis, and this effect is blocked by D-Lys3-GHRP-6. Furthermore, ghrelin reduced RANKL/OPG ratio thus contrasting osteoclastogenesis. Accordingly, conditioned media from rOB treated with ghrelin decreased the number of multinucleated TRAcP+ cells as compared with the conditioned media from untreated-control rOB. Our data suggest new roles for ghrelin in modulating bone homeostasis via a specific interaction with GHSR-1a in osteoblasts with subsequent enhancement of both β-catenin levels and OPG expression.

Ghrelin is required for dietary restriction-induced enhancement of hippocampal neurogenesis: lessons from ghrelin knockout mice.

Neurogenesis occurs in the adult hippocampus and is enhanced by dietary restriction (DR), and neurogenesis enhancement is paralleled by circulating ghrelin level enhancement. We have previously reported that ghrelin modulates adult neurogenesis in the hippocampus. In order to investigate the possible role of ghrelin in DR-induced hippocampal neurogenesis in adult mice, ghrelin knockout (GKO) mice and wild-type (WT) mice were maintained for 3 months on DR or ad libitum (AL) diets. Protein levels of ghrelin in the stomach and the hippocampus were increased by DR in WT mice. One day after BrdU administration, the number of BrdU-labeled cells in the hippocampal dentate gyrus was decreased in GKO mice maintained on the AL diet. DR failed to alter the proliferation of progenitor cells in both WT and GKO mice. Four weeks after BrdU injection, the number of surviving cells in the dentate gyrus was decreased in AL-fed GKO mice. DR increased survival of newborn cells in WT mice, but not in GKO mice. Levels of brain-derived neurotrophic factor protein in the hippocampus were similar between WT and GKO mice, and were increased by DR both in WT and GKO mice. These results suggest that elevated levels of ghrelin during DR may have an important role in the enhancement of neurogenesis induced by DR.

Ghrelin Is a Novel Regulator of GLP-1 Secretion.

GLP-1 is a gastrointestinal L-cell hormone that enhances glucose-stimulated insulin secretion. Hence, strategies that prevent GLP-1 degradation or activate the GLP-1 receptor are used to treat patients with type 2 diabetes. GLP-1 secretion occurs after a meal and is partly regulated by other circulating hormones. Ghrelin is a stomach-derived hormone that plays a key role in whole-body energy metabolism. Because ghrelin levels peak immediately before mealtimes, we hypothesized that ghrelin plays a role in priming the intestinal L-cell for nutrient-induced GLP-1 release. The intraperitoneal injection of ghrelin into mice 15 min before the administration of oral glucose enhanced glucose-stimulated GLP-1 release and improved glucose tolerance, whereas the ghrelin receptor antagonist D-Lys GHRP-6 reduced plasma levels of GLP-1 and insulin and diminished oral glucose tolerance. The ghrelin-mediated improvement in glucose tolerance was lost in mice coinjected with a GLP-1 receptor antagonist as well as in Glp1r(-/-) mice lacking the GLP-1 receptor. The impaired oral glucose tolerance in diet-induced obese mice was also improved by ghrelin preadministration. Importantly, ghrelin directly stimulated GLP-1 release from L-cell lines (murine GLUTag, human NCI-H716) through an extracellular signal-related kinase 1/2-dependent pathway. These studies demonstrate a novel role for ghrelin in enhancing the GLP-1 secretory response to ingested nutrients.

The role of ghrelin in metabolic regulation.

To discuss recent research on the role of ghrelin in the regulation of carbohydrate and lipid metabolism in the context of its wider role in regulating energy balance. Ghrelin possesses a range of centrally and peripherally mediated metabolic actions influencing insulin glucose homeostasis and fatty acid metabolism and appetite. Although acyl ghrelin was previously thought to be the active hormone, recent evidence suggests that des-acyl ghrelin also possesses activity, and the enzyme ghrelin-O-acyl transferase regulates their interconversion. In partnership with insulin and leptin, ghrelin defends against energy deficit by enhancing hunger, conserving carbohydrate and promoting fat oxidation. In the postprandial state, it contributes to satiety, energy storage and favours glucose oxidation. New research suggests a range of new roles including addictive behaviours, cardiovascular protection, neuroprotection and regeneration and perhaps the ageing process. Ghrelin functions primarily as a short-term metabolic switch at the onset of fasting, gearing the fuel economy away from glucose uptake, conserving glucose for vital functions, favouring fatty acid oxidation and triggering food-seeking behaviour. The ghrelin system is a potential target for a range of pharmacological interventions, but its pleiotropic nature makes selective treatments challenging.

Plasma Ghrelin Concentrations Are Negatively Correlated With Urine Albumin-to-Creatinine Ratio in Newly Diagnosed Type 2 Diabetes

BackgroundAging is associated with a decrease in appetite, energy intake and glucose tolerance. Experimental studies have suggested that ghrelin and obestatin play a role in glucose homeostasis and in the regulation of energy metabolism. However, few studies have been performed on the role of ghrelin and obestatin in middle-aged and old adults. MethodsIn the present study, we investigated the plasma concentrations of ghrelin and obestatin in middle-aged (41-64 years) and old (65-76 years) subjects with newly diagnosed type 2 diabetes mellitus (NDD) and normal glucose tolerance (NGT). We also characterized the relationship among plasma ghrelin and obestatin levels and glucose/lipid metabolism. The fasting plasma ghrelin and obestatin concentrations were analyzed using enzyme immunoassay method. ResultsPlasma obestatin concentrations in diabetic subjects were significantly lower than those in NGT subjects. Plasma ghrelin were negatively associated with fasting glucose, hemoglobin A1c, urine albumin-to-creatinine ratio (UACR) and positively correlated with high-density lipoprotein cholesterol. In addition, plasma obestatin level was correlated negatively with systolic blood pressure, triglycerides and total cholesterol. Furthermore, multiple regression analysis indicated that UACR was a significantly independent predictor of fasting plasma ghrelin levels. ConclusionsCollectively, ghrelin and obestatin levels may be markers reflecting glucose and lipid conditions in NDD. The lower ghrelin levels may be a potential indicator for renal dysfunction in patients with type 2 diabetes mellitus.

Review of novel aspects of the regulation of ghrelin secretion.

The role of ghrelin in regulating metabolism and energy balance has been a subject of intense focus ever since its discovery. Ghrelin regulates energy balance in the short term by induction of appetite and in the longer term by increasing body weight and adiposity. It is the only known peripheral orexigenic hormone and one of the most potent endogenous orexigenic factors discovered to date. However, whilst extensively studied, the mechanism of ghrelin secretion is not well understood. A better understanding of the pathways controlling ghrelin secretion could be useful in the development of new therapeutic approaches to appetite-related disorders. Here, we discuss current knowledge of the processes that control ghrelin secretion, focusing on neural, chemical and hormonal stimuli. In addition, we share our view on the potential of targeting ghrelin for the treatment of eating disorders such as obesity, anorexia nervosa and cachexia.