Genetic Variation of the Ghrelin Signaling System in Females With Severe Alcohol Dependence
Sara LandgrenElisabet JerlhagJarmila HallmanLars OrelandLauren LissnerElisabeth StrandhagenDag S. ThelleHenrik ZetterbergKaj BlennowJörgen A. Engel
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Introduction: Central ghrelin signaling is required for the rewarding effects of alcohol in mice. Because ghrelin is implied in other addictive behaviors such as eating disorders and smoking, and because there is co‐morbidity between these disorders and alcohol dependence, the ghrelin signaling system could be involved in mediating reward in general. Furthermore, in humans, single nucleotide polymorphisms (SNPs) and haplotypes of the pro‐ghrelin gene (GHRL) and the ghrelin receptor gene ( GHSR ) have previously been associated with increased alcohol consumption and increased body weight. Known gender differences in plasma ghrelin levels prompted us to investigate genetic variation of the ghrelin signaling system in females with severe alcohol dependence ( n = 113) and in a selected control sample of female low‐consumers of alcohol from a large cohort study in southwest Sweden ( n = 212). Methods: Six tag SNPs in the GHRL (rs696217, rs3491141, rs4684677, rs35680, rs42451, and rs26802) and four tag SNPs in the GHSR (rs495225, rs2232165, rs572169, and rs2948694) were genotyped in all individuals. Results: We found that one GHRL haplotype was associated with reports of paternal alcohol dependence as well as with reports of withdrawal symptoms in the female alcohol‐dependent group. Associations with 2 GHSR haplotypes and smoking were also shown. One of these haplotypes was also negatively associated with BMI in controls, while another haplotype was associated with having the early‐onset, more heredity‐driven, type 2 form of alcohol dependence in the patient group. Conclusion: Taken together, the genes encoding the ghrelin signaling system cannot be regarded as major susceptibility genes for female alcohol dependence, but is, however, involved in paternal heritability and may affect other reward‐ and energy‐related factors such as smoking and BMI.Keywords:
Alcohol Dependence
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Obestatin
To investigate the role of ghrelin and obestatin in obesity mechanisms.A total of 88 obese children and 25 normal children were enrolled. Moreover, 46 obese children took part in a summer camp for weight reduction. Fasting ghrelin, obestatin and other biochemical parameters were measured in all subjects and re-measured in 45 obese children finishing the camp.The ghrelin levels in the control and obese groups were 67.26 +/- 23.41 pmol/L and 56.53 +/- 15.97 pmol/L with a significant difference (p = 0.039), while the obestatin levels (89.41 +/- 23.63 vs. 83.13 +/- 17.21 pmol/L) were not significantly different (p = 0.083). The ghrelin/obestatin ratio in the controls was significantly higher than that in the obese group (p = 0.014). In the latter, fasting insulin and alanine aminotransferase were independent factors for ghrelin; fasting insulin, weight and gender were independent factors for obestatin and alanine aminotransferase was an independent factor for ghrelin/obestatin. Moreover, ghrelin, obestatin and ghrelin/obestatin increased after weight reduction (p < 0.05, respectively), and the increment in ghrelin and obestatin was associated with a decrement in insulin resistance.These data suggest that ghrelin, obestatin and/or the ghrelin/obestatin ratio are associated with obesity in childhood.
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Ghrelin gene can generate various bioactive molecules besides Ghrelin.In this review,not only the Ghrelin derived peptide were introduced,but the physiological functions,distributions and the factors which affect secretion of Des-acyl ghrelin and Obestatin were reviewed.This paper aimed to provide theoretical basis for future researches on Des-acyl ghrelin and Obestatin in the field of animal production.
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Obesity has increasingly become a major medical and public health burden in both developed and developing countries. Numerous hormones are involved in controlling appetite and food intake via the neuro-humoral gut-brain axis and several peptides that are synthesized and secreted from the gut have been recently investigated in order to determine their effects on food intake and satiety. Ghrelin is an appetite-stimulating peptide that rises in the fasted state causing increases in food intake. Obestatin is a newly discovered hormone encoded by the same gene as ghrelin, and its putative role in the regulation of appetite and metabolism is unclear. A number of studies using animal models have shown that obestatin opposes the effects of ghrelin on food intake whilst others found that obestatin has little if any affect on gastrointestinal motility, or on food intake. There are also controversies to the receptor mediating obestatin effects with the previously orphan G protein coupled receptor GPR39 suggested to be the main candidate. Investigating the molecular mechanism underlying obestatin and other gut hormones involved in appetite regulation may prove to be useful in finding new strategies to treat obesity. Keywords: Ghrelin, obestatin
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Background Ghrelin and obestatin are two gastric hormones encoded by the same preproghrelin gene that convey information concerning nutritional status to the central nervous system. Ghrelin has been considered as an appetite stimulating peptide that has a role in the regulation of energy homeostasis. Obestatin has been described for its appetite suppressing effects opposing ghrelin's effect on food intake. The study aimed to evaluate ghrelin, obestatin and the ghrelin/obestatin ratio in obese children compared to non-obese and correlate them to food macronutrients intake. Methods This study is a cross-sectional case control study comprising 60 obese children, in addition to 31 age- and sex-matched controls. All children were subjected to clinical examination, anthropometric assessment, and a 3-day 24-h dietary recall. Fasting serum ghrelin and obestatin levels were evaluated, the ghrelin/obestatin ratio was calculated and they were correlated to macronutrients intake. Results Obese children had significantly lower serum fasting levels of ghrelin, obestatin and the ghrelin/obestatin ratio than the control group. The mean intake of total energy and macronutrients was significantly higher in obese children. Ghrelin showed positive correlation with total energy and fat intake in the obese group. Obestatin had positive correlations with total energy and fat intake while the ghrelin/obestatin ratio had a negative correlation with the total energy intake in the control group. Conclusions Ghrelin, obestatin and the ghrelin/obestatin ratio were significantly lower in obese children and significantly associated with their total energy intake. Disturbed ghrelin to obestatin balance may have a role in the etiology and pathophysiology of obesity.
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Background: Obestatin and ghrelin are two gastric hormones that have a potential role in dietary intake regulation. Obestatin/ghrelin ratio has been proposed as activity markers in obesity. The study aimed to evaluate ghrelin, obestatin and the ghrelin/obestatin ratio in obese compared to control subjects and to determine their relationship with anthropometric and metabolic parameters. Methods: Fasting obestatin and ghrelin levels were measured using enzyme-linked immunosorbent assay ELISA in 28 obese and 24 healthy subjects. The fasting ghrelin/obestatin ratio was calculated. Anthropometric and metabolic parameters were also assessed. Results: Obese patients had significantly lower obestatin and ghrelin blood levels compared with controls. The Ghrelin/Obestatin ratio was significantly lower in obese group 0.813±0.0417 ng/ml than in the control group 0.896±0.049 ng/ml, (p<0.001). In obese patients, obestatin and ghrelin were significantly and negatively correlated with BMI and positively correlated with HDL-C. Conclusion: Circulating preprandial ghrelin to obestatin ratio is decreased obese subjects. We suggest that low preprandial ghrelin to obestatin ratio may be involved in the etiology and pathophysiology of obesity.
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三肽， ghrelin， des 酰 ghrelin 和 obestatin 从普通专业版荷尔蒙被导出， preproghrelin 由张贴翻译处理，在胃从内分泌的房间发源。检验这些肽的效果，我们在自由地感动有意识的老鼠模特儿使用了胃肠的活动性的压力计的测量。Ghrelin 在美联储和动物的 fasted 状态在窦和十二指肠的活动性上施加 stimulatory 效果。Des 酰 ghrelin 处于动物的 fasted 状态在窦的活动性上，然而并非在十二指肠的活动性上施加禁止的效果。Obestatin 处于喂的状态，然而并非处于动物的 fasted 状态在窦和十二指肠的活动性上施加禁止的效果。在大脑的 NPY Y2 或 Y4 受体可以调停 ghrelin 的行动，在大脑的 CRF 类型 2 受体调停 des 酰 ghrelin 的行动，而 CRF 录入 1 和类型 2 受体，大脑调停 obestatin 的行动。迷走神经传入路径可能涉及 ghrelin 的行动，然而并非在 des 酰 ghrelin 的行动包含了，而迷走神经传入路径力量部分涉及 obestatin 的行动。
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Circulating Ghrelin Levels and Obestatin/Ghrelin Ratio as a Marker of Activity in Ulcerative Colitis
Background/Aims Ghrelin levels are known to increase in patients with ulcerative colitis (UC), but serum obestatin levels in UC patients are not well elucidated. The aim of this study was to examine the relationship between serum ghrelin and obestatin levels and disease activity in UC patients. Methods The serum ghrelin and obestatin levels were measured in 21 UC patients (12 with active disease and 9 in remission) using enzyme-linked immunosorbent assay. The relationship between the circulating levels of these 2 hormones and disease activity was analyzed. The colonic mucosal mRNA expression of ghrelin and obestatin was measured by quantitative reverse transcription polymerase chain reaction. Results The mean serum ghrelin values were significantly higher in patients with active disease than in patients with remission (1370.6±404.3 vs. 783.5±235.3 pg/mL, P=0.001). Colonic mucosal mRNA expression of ghrelin was also significantly higher in patients with active disease than in patients in remission (0.805±0.214 vs. 0.481±0.356, P=0.018). However, the mean serum obestatin levels and colonic mucosal mRNA expression of obestatin were not significantly different between both groups. The circulating obestatin/ghrelin ratio was significantly lower in patients with active UC than in patients in remission (0.32±0.08 vs. 0.58±0.20, P=0.001). Conclusions The serum ghrelin levels and the obestatin/ghrelin ratio were related to the activity of UC, but serum obestatin was not related to activity of UC. The ghrelin levels and the obestatin/ghrelin ratio could serve as activity markers in patients with UC. Keywords: Colitis, ulcerative; Disease activity; Ghrelin; Obestatin; Ratio
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Obestatin is described as an anorexigenic peptide, and has adverse effects of ghrelin. It has no inhibitory effects on acute/chronic food intake, and it has been reported by several researchers. The role of obestatin in metabolism is still not clear. In the present study, the purpose is to determine the effects of chronically administrated obestatin. For this purpose, (1 µmol/kg; i.p.) or ghrelin (1 µmol/kg; i.p.) and food restriction (24h fast:24h fed) on plasma obestatin, ghrelin, leptin, insulin, cholecystokinin (CCK) and glucose levels, and body weight gain were investigated for 14 days in mice. Additionally, mice were treated with acute ip (100 nmol/kg) injections of obestatin or ghrelin to investigate the food consumptions, plasma obestatin and ghrelin levels to determine unknown acute effects of obestatin. Plasma ghrelin levels increased significantly in obestatin administered mice when compared with the control group for chronic treatment. This increase is consistent with immunohistochemical findings which claim that the number of ghrelin and obestatin immunopositive cells in fundus tissue of stomach are considerably high in obestatin treated animals. Plasma obestatin and ghrelin levels has shown an increase endogenously in food restricted mice, but plasma leptin and insulin levels have been found to be lower compared to the control group. Acute administration of obestatin caused a decrease in plasma obestatin level at 60 min after injection and had no effect on the reduction of food intake in each treatment time. These results imply that obestatin may not itself be involved in the metabolism regulation; however, obestatin accompanied by ghrelin may play a role in the long-term regulation of metabolism.
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