• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.43-48
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• 2012

Glutamate excitotoxicity is emerging as a contributor to degeneration of spinal cord motoneurons in amyotrophic lateral sclerosis (ALS). Recently, we have reported that ghrelin protects motoneurons against chronic glutamate excitotoxicity through the activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-$3{\beta}$ pathways. Previous studies suggest that activated microglia actively participate in the pathogenesis of ALS motoneuron degeneration. However, it is still unknown whether ghrelin exerts its protective effect on motoneurons via inhibition of microglial activation. In this study, we investigate organotypic spinal cord cultures (OSCCs) exposed to threohydroxyaspartate (THA), as a model of excitotoxic motoneuron degeneration, to determine if ghrelin prevents microglial activation. Exposure of OSCCs to THA for 3 weeks produced typical motoneuron death, and treatment of ghrelin significantly attenuated THA-induced motoneuron loss, as previously reported. Ghrelin prevented THA-induced microglial activation in the spinal cord and the expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ and interleukin-$1{\beta}$. Our data indicate that ghrelin may act as a survival factor for motoneurons by functioning as a microglia-deactivating factor and suggest that ghrelin may have therapeutic potential for the treatment of ALS and other neurodegenerative disorders where inflammatory responses play a critical role.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.4
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• pp.195-200
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• 2004

Ghrelin is a newly discovered peptide, which is released from the stomach and neurons in the hypothalamic arcuate nucleus (ARC), and potently stimulates growth hormone release and food intake. In the present study, we investigated the effect of ghrelin on $[Ca^{2+}]_i$ in thyroid FRTL-5 cells. Ghrelin (5 nM) increased $[Ca^{2+}]_i$ and TSH (1 unit/l) had an additive effect on $[Ca^{2+}]_i$ when extracellular normal solution was 1.1mM $Ca^{2+}$ containing Coon's modified Ham's F12 medium. When $Ca^{2+}-free$ medium containing 2 mM EGTA replaced the above normal solution, ghrelin also induced a similar rise in $[Ca^{2+}]_i$. In the middle of $[Ca^{2+}]_i$ increment by ghrelin, nifedipine $(1\;{\mu}M)$, nickel $(100\;{\mu}M)$ and $La^{3+}\;(100\;{\mu}M)$ had no effect on $[Ca^{2+}]_i$. After endoplasmic reticulum was depleted by cyclopiazonic acid $(CPA;10\;{\mu}M)$, ghrelin caused no visible change on $[Ca^{2+}]_i$ in $Ca^{2+}-free$/2 mM EGTA solution. These results suggest that ghrelin can increase $[Ca^{2+}]_i$ through endoplasmic reticulum in thyroid FRTL-5 cells.

• The Korean Journal of Food And Nutrition
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• v.27 no.2
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• pp.225-230
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• 2014

The objective of this study was to investigate the effects of soy hydrolysate fractions on appetite suppression and ghrelin releasing. In a short-term experiment, the cumulative food intake and serum ghrelin level were decreased significantly (p<0.05) during a 4-hr period after the interperitoneal injection of soy hydrolysate fractions (0.5, 1 g/kg BW), following a 12-hr period of food deprivation. In a long-term experiment, food efficiency ratio (FER) was also reduced significantly (p<0.05), when soy hydrolysate fractions (0.5, 1% in drinking water) were given orally for 8 wks. Therefore, we found that soy hydrolysate fractions affected food intake through appetite and ghrelin releasing in short-term and long-term experiments. In conclusion, this study indicated that soy hydrolysate fractions would diminish the sensation of hunger by reducing the secretion of orexigenic factors such as ghrelin that send satiety signals to the brain, terminating food intake.

• Clinical and Experimental Pediatrics
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• v.48 no.10
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• pp.1068-1075
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• 2005

Purpose : The role of ghrelin, which promotes the secretion of growth hormone, was not well known until now. Recently it was found that the mutation of ghrelin gene is related to obesity and diabetes. This study is to find the screening method that can easily and effectively detect the polymorphism of Leu72Met in ghrelin gene of obesity patients and apply it to clinical usage. Methods : We compared PCR-RFLP, PCR-SSCP and ARMS methodologies for analyzing of the polymorphism of Leu72Met in ghrelin gene of obesity children, and also studied the merits and demerits of these methodologies. Results : In this study, we were able to find out the band of peculiar allele of Leu72Met in ghrelin gene using PCR-RFLP, PCR-SSCP and ARMS analyses. The polymorphism of Leu72Met in ghrelin gene determined by all above methodologies was in complete agreement. Compared to the PCR-RFLP and PCR-SSCP, ARMS analysis is simple, inexpensive and also consume less time. It is very sensitive to analyze the polymorphism and easy to understand the results of test. Conclusion : Though PCR-RFLP, PCR-SSCP and ARMS analyses were sensitive to analyze the polymorphism of Leu72Met in ghrelin gene, ARMS analysis appears to be more efficient than PCR-RFLP and PCR-SSCP. Therefore, we conclude that ARMS analysis is suitable to analyze the polymorphism of Leu72Met in ghrelin gene for large quantity of specimens.

• Clinical and Experimental Pediatrics
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• v.50 no.9
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• pp.905-911
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• 2007

Purpose : Ghrelin, being secreted from the stomach, stimulates growth hormone secretion and controls energy homeostasis by increasing appetite. Leptin, being secreted from the adipocytes, controls weight and energy homeostasis by decreasing appetite. Leptin concentration is reported to increase after childhood cancer therapy. This study was aimed to compare ghrelin and leptin concentrations in normal children and children who received cancer therapy. Methods : We enrolled forty-three patients who were diagnosed with cancer and received radiotherapy or chemotherapy during Dec. 2004 through Dec. 2005 in St. Marys hospital and Kangnam St. Marys hospital. Forty-five healthy children were selected as a control group whose age, gender, weight and height were similar to those of cancer group. The serum leptin and ghrelin concentrations were also measured by radioimmunoassay. Results : The cancer group showed higher BMI and leptin concentrations. The control group showed higher concentrations of ghrelin. Both control and cancer groups revealed positive correlations between leptin concentrations and BMI. Ghrelin concentrations in the control group showed negative correlations with age, height, weight and BMI but no significant correlation was found in the cancer group. All the parameters in the group treated with chemotherapy only were not different from those in the group treated with chemotherapy and irradiation. But the level of ghrelin in the acute myeloid leukemia group was much higher than those in the acute lymphoblastic leukemia group. Conclusion : Patients with pediatric cancer treatment have presented higher BMI and leptin concentrations but lower ghrelin concentrations than those in healthy children. Because of the relatively short duration and cross sectional method of the study, however, further long term and prospective study will be required in the future.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.6
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• pp.861-867
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• 2008

The objective of this study was to evaluate the effect of exogenous ghrelin on the behaviors, weight gain, and feed intakes of weanling piglets. A total of 25 pairs of Duroc$\times$Landrace$\times$Large White piglets weaned at 21 days of age were used in this experiment which finished on day 36. Each pair of healthy piglets from the same litter with similar body weight and of the same gender were selected and randomly arranged to ghrelin or control groups. Thus, there were 50 piglets (ghrelin 25; control 25) kept in 10 pens (ghrelin 5; control 5) and 5 piglets per pen. Initial body weight of the pigs did not differ between the control and ghrelin treatment ($7.43{\pm}0.17kg$; p = 0.81). Experimental pigs were infused with ghrelin ($1{\mu}g/d$ pig) via the marginal ear vein between 0750 and 0800 h at 22, 23, 24 days of age. Control pigs were infused with 0.9% saline. Feed consumption was measured on days 23, 24, 25, 29 and 36. Body weight was measured on days 22, 23, 24, 25, 29 and 36. Behavior data of individual piglets were collected by real-time observation from 0800-1500 h through remote supervisory equipment at 22, 23 and 24 days of age. The results indicated that ghrelin infusion could increase drinking (p<0.05) and lying behaviors (p<0.01) and decrease mounting behaviors (p<0.05). No significant influence of ghrelin was found on average daily weight gain (ADG) and average daily feed intake (ADFI) in this experiment (p>0.05). In conclusion, exogenous ghrelin by the method above and at the dosage of $1{\mu}g/d$ pig could cause a variety of behavioral effects, but not improve performance of weanling piglets.

• BMB Reports
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• v.41 no.1
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• pp.55-61
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• 2008

Ghrelin and obestatin are a single gene products and are a multiple functional peptides that regulates energy homeostasis, and food intake. In the present work, we studied the secretion of ghrelin and its co-secreted peptide obestatin in 44 patients with ischemic heart disease with that of 27 healthy matched controls. Here we first conducted using an immunohistochemistry assay to screen whether human salivary glands have any obestatin immunoreactivity. Then, serum and saliva obestatin and acylated ghrelin levels were determined by using Radioimmunoassay. Our immunohistochemical analysis demonstrated that obestatin was localized in the striated and excretory duct of human salivary gland. We also report for the first time that obestatin, like ghrelin, is present in human salivary gland and saliva. No evidence of the role of obestatin or ghrelin saliva levels in the context of ischemic heart disease was found. Salivary ghrelin and obestatin levels are correlated in controls with the blood levels. Determination of salivary values could represent a non-invasive alternative to serum ones that can be useful in clinical practice.

• Nutrition Research and Practice
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• v.4 no.4
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• pp.311-316
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• 2010

The purpose of this study was to investigate the relationship between birth weight and appetite related hormones, insulin resistance, and antioxidant status in overweight children aged 9-10 years. Thirty-four healthy overweight children (18 boys, 16 girls) were evaluated with respect to anthropometric measurement, lipid profiles, leptin, ghrelin, glucose, insulin, C-peptide, lipid soluble vitamins, and antioxidant enzyme activities. I found that birth weight was negatively correlated with insulin resistance parameters, ghrelin, and coenzyme Q10 levels. There was a significant positive correlation between present BMI and leptin level, while a negative correlation was noted between the BMI and $\alpha$-tocopherol and lycopene levels. When total subjects were classified into three groups by tertiles of birth weight, the lowest tertile of birth weight (LTB) group showed higher levels of fasting glucose, HOMA-IR, and ghrelin level than the highest tertile of birth weight (HTB) groups. On the other hand, HTB group showed an increased oxidative stress (decreased coenzyme Q10 level and catalase activity) compared to the LTB group. In conclusion, plasma ghrelin level might play an important role in accelerated growth in overweight children with LTB. Increased insulin resistance is present in overweight children with LTB, while decreased coenzyme Q10 and catalase activity in overweight children with HTB. These results suggest that birth weight might be an important factor for determination of treatment for obesity related complications in childhood obesity.

• BMB Reports
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• v.40 no.1
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• pp.29-35
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• 2007

During the past decade, many salivary parameters have been used to characterize disease states. Ghrelin (GAH) is recently-discovered peptide hormone secreted mainly from the stomach but also produced in a number of other tissues including salivary glands. The aim of this work was to examine the relationship between active (aGAH) and inactive (dGAH) ghrelin in the saliva and other salivary parameters in type II diabetic patients and healthy controls. Salivary parameters were assessed in a single measurement of unstimulated whole saliva from 20 obese and 20 non-obese type II diabetes patients, and in 22 healthy controls. Total protein and alpha-amylase were determined by colorimetric methods, and glucose by the glucose-oxidase method. Saliva aGAH and dGAH levels were measured using a commercial radioimmunoassay (RIA) kit. Salivary concentrations of aGAH and dGAH ghrelin were more markedly decreased in obese diabetic subjects than in the two other groups. Glucose and alpha-amylase levels were higher in diabetic subjects than in controls. Furthermore, there were correlations between GAH levels and BMI, and between GAH and blood pressure. However, there was no marked variability in saliva flow rates among the groups. These results indicate that measurement of salivary GAH and its relationship to other salivary parameters might help to provide insight into the role of ghrelin in diabetes.

• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.238-245
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• 2005

Purpose: Ghrelin, produced primarily in the gastrointestinal tract, including the stomach, has been reported to reflect nutritional status and to control homeostasis by influencing food intake and adiposity. The purpose of this study is to evaluate nutritional status, as well as plasma and gastric tissue ghrelin levels, in patients with gastric cancer who underwent a gastrectomy. Materials and Methods: Eighty patients were analyzed by the degree of weight loss $(weight\;loss{\geq}5%\;or\;<5%)$ and the extent of gastrectomy (subtotal or total gastrectomy). Blood samples were collected from all patients preoperatively and postoperatively especially at seven days. Gastric tissues, including tumor and normal tissues, were obtained from the resected stomach. levels of plasma and tissue ghrelin were measured with a commercial ELISA kit. Results: There were no significant differences in the clinical characteristics and ghrelin levels of plasma, gastric tumor tissue and normal tissue by the degree of weight loss. The ghrelin levels in plasma and tumor tissue showed no correlations with each other while the ghrelin level in tumor tissue was significantly lower than that in normal tissue. The degree of cellular differentiation also had an association with ghrelin production. A gastrectomy proved to decrease significantly plasma ghrelin levels, body mass index, and biochemical markers, regardless of the extent of gastric resection. Conclusion: These results show that gastric cancer affects the production of ghrelin in the gastric mucosa and that ghrelin is mainly produced in stomach even though it could be partially covered by endogenous ghrelin from other organs following a gastrectomy. However, we should further investigate which other factors have an impact on energy consumption, ghrelin secretion, and changes in ghrelin levels after a gastrectomy.