2형 당뇨병 환자에서 혈청 Ghrelin의 농도

장용석,황동진,양윤정,박지현,이대열 대한소아내분비학회 2004 Annals of Pediatirc Endocrinology & Metabolism Vol.9 No.1

Characteristics of Gene Structure of Bovine Ghrelin and Influence of Aging on Plasma Ghrelin

Kita, K.,Harada, K.,Nagao, K.,Yokota, H. Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.5

Ghrelin is a novel growth-hormone-releasing acylated peptide, which has been purified and identified in rat stomach. In the present study, the full-length sequence of bovine ghrelin cDNA was cloned by RT-PCR. The bovine ghrelin cDNA sequence derived in the present study included a 348 bp open reading frame and a 137 bp 3'UTR. The putative amino acid sequence of bovine prepro-ghrelin consisted of 116 amino acids, which contained the 27-amino acid ghrelin. The sequence analysis of the bovine ghrelin gene revealed that an intron existed between Gln$^{13}$ and Arg$^{14}$ of ghrelin. This exon-intron boundary matched the GT-AG rule of the splicing mechanism. Compared with rats, which have two tandem CAG sequences in the 3'end of intron, bovine ghrelin genome has only one CAG sequence. Therefore, although rats can produce 28 amino acid-ghrelin and 27 amino acid-des-Gln$^{14}$-ghrelin by alternative splicing, ruminant species, including bovines, might be able to produce only one type of ghrelin peptide, des-Gln$^{14}$-ghrelin. The influence of aging on plasma ghrelin concentration was also examined. Plasma ghrelin concentration increased after birth to approximately 600 days of age, and then remained constant.

발생에 따른 흰쥐의 위에서의 ghrelin mRNA의 발현 변화

조미행(Mi Haeng Cho),이상혁(Sang Hyuk Lee),김남희(Nam-Hee Kim),손현준(Hyun Joon Sohn),박정현(Jeonghyun Park),황승준(Seung Jun Hwang),김민선(Min-Seon Kim),박경한(Kyeong Han Park) 대한해부학회 2003 Anatomy & Cell Biology Vol.36 No.3

Ghrelin은 growth hormone secretagogue로서 28개의 아미노산으로 구성된 펩티드호르몬이다. 성장호르몬 분비의 자극, 식욕의 조절, 위산 분비의 자극 등을 일으키는 것으로 알려진 ghrelin은 위, 뇌하수체, 작은창자 등에서 합성되며 특히 위에서 발생과정에 따라 그 분비 양상의 변화가 있음이 알려져 있으나 발생시기와 노화에 따른 ghrelin mRNA 발현에 대한 형태학적 연구는 없는 실정이다. 본 연구에서는 digoxigenin으로 표지한 oligonucleotide를 이용하여 발생시기별 Sprague-Dawley계 흰쥐에서 적출한 위 조직에 ghrelin mRNA에 대한 in situ hybridization을 시행하고 ghrelin mRNA 양성세포의 분포를 조사하였다. Ghrelin 양성세포는 임신 제18일 태아의 위에서는 관찰되지 않았으나 출생후 점진적으로 증가하여 6주에서 가장 많은 수의 양성세포가 관찰되었다. 이후에 양성세포의 숫자가 다시 감소하여 18월에 이르러 통계적으로 유의한 수준으로 감소하였다. Ghrelin 양성세포는 주로 위의 fundus 부위에 분포하였으며 발생 초기에는 위샘의 바닥부분에 소수가 분포하다가 발생이 진행됨에 따라 위샘의 윗부분까지 확산되어 분포하였다. 관찰된 양성세포는 대부분이 closed-type의 내분비세포였다. Ghrelin 양성세포는 발생 과정에 따라 그 분포와 숫자에 변화가 있었으며 사춘기에 가장 많은 숫자의 양성세포가 존재하였고 노화과정에 따라 다시 감소한 사실로 미루어 위에서의 ghrelin의 발현이 성장과 노화에 관련이 있는 것으로 추정된다. Ghrelin is a recently identified member of growth hormone secretagogue, which is synthesized as peptide of 28 amino acids in stomach, pituitary and intestines. Ghrelin controls food intake, and induces gastric acid secretion. It has been reported that synthesis and secretion of ghrelin changes according to age of animals. In this study, in situ hybridization technique with digoxigenin-labeled oligonucleotide probe is applied to elucidate the developmental change of ghrelin mRNA expression pattern in rat stomach. Ghrelin mRNA positive cells first appeared in stomach of 9 day rats, mainly in base of gastric glands. It showed the highest density and spread to neck area of the gastric gland in 6 week rats. Number of positive cells decreased significantly in 18 months. Most of ghrelin mRNA positive cells were found as closed-type endocrine cells in fundus area. These results suggest that ghrelin expression may be involved in development and ageing process.

Ghrelin suppresses tunicamycin- or thapsigargin-triggered endoplasmic reticulum stress-mediated apoptosis in primary cultured rat cortical neuronal cells

Chung, Hyunju,Chung, Ho-Yeon,Bae, Chong Woo,Kim, Chong-Jin,Park, Seungjoon The Japan Endocrine Society 2011 Endocrine journal Vol.58 No.5

<P>Ghrelin functions as a neuroprotective agent and rescues neurons from various insults. However, the molecular mechanisms underlying ghrelin neuroprotection remains to be elucidated. An accumulation of unfolded proteins in the endoplasmic reticulum (ER) leads to ER stress and then induces ER stress-mediated cell death. Here, we report that acylated ghrelin inhibited tunicamycin- or thapsigargin-triggered ER stress-induced apoptotic cell death in primary rat cortical neurons. An analysis using a specific inhibitor of phosphatidylinositol-3-kinase (PI3K), LY294002, showed that ghrelin prevented apoptosis via the activation of PI3K signaling pathway. Ghrelin suppressed tunicamycin- or thapsigargin-induced upregulation and nuclear translocation of C/EBP homologous protein (CHOP). Ghrelin also inhibited tunicamycin or thapsigargin induction of PRK-like ER kinase (PERK), eukaryotic translation initiation factor-2α (eIF2α) and activating transcription factor (ATF) 4. Exposure of cells to tunicamycin or thapsigargin resulted in nuclear translocation of forkhead box protein O1 (Foxo1), which was reduced by pretreatment with ghrelin. The protective effect of ghrelin was accompanied by an increased phosphorylation of Akt and glycogen synthase kinase (GSK)-3β. Furthermore, ghrelin phosphorylated and inactivated pro-apoptotic BAD and Foxo1. In addition, phospho-Akt was translocated to the nucleus in response to ghrelin and PI3K inhibition by LY294002 prevented ghrelin-induced effect on phospho-Akt localization. Our study suggests that suppression of CHOP activation via the inhibition of PERK/eIF2α/ATF4 pathway and prevention of Foxo1 activation and nuclear translocation may contribute to ghrelin-mediated neuroprotection during ER stress responses. Our data also suggest that PI3K/Akt-mediated inactivation of GSK-3β, BAD and Foxo1 may be associated with the anti-apoptotic effect of ghrelin.</P>

비만 여성에서 운동 전후 혈장 Ghrelin 농도의 변화

이대열,강은영,김민선,박은혜,김기진 대한소아내분비학회 2007 Annals of Pediatirc Endocrinology & Metabolism Vol.12 No.2

Purpose : Ghrelin is the known orexigenic hormone as well as an endogenous ligand for the growth hormone secretagogue receptor and has been shown to be related with the regulation of energy homeostasis. To investigate the changes of plasma ghrelin levels in response to weight loss induced by exercise, we measured fasting plasma ghrelin levels in obese and control groups before and after exercise intervention. Methods : According to body mass index (BMI), total 32 adult women were divided into obese group (n=14, BMI≥25 kg/m2) and control group (n=18, BMI<25 kg/m2). All subjects underwent weight reduction exercise intervention for 3 months. Before and after exercise, we measured body compositions, serum lipid profiles, serum glucose, plasma ghrelin levels in all subjects. Results : At baseline, the plasma ghrelin levels in obese group were significantly lower than those in the control group. After the exercise intervention, the plasma ghrelin levels increased significantly from 174.8±40.8 to 235.9±53.1 pg/mL (P<0.05) in obese group and from 244.4±42.6 to 276.5±45.1 pg/mL (P< 0.05) in control group. The changes of plasma ghrelin levels in obese group (38.7±30.8 pg/mL) were significantly higher than those of the control group (14.6±20.3 pg/mL, P<0.05). However, there was no significant relationship between the changes of plasma ghrelin levels and various parameters in the obese group after exercise. Conclusion : In this study, the plasma ghrelin levels in obese adults were significantly increased than those in the control group associated with exercise-induced weight loss. Further studies are needed to establish the precise roles of ghrelin in the regulation of energy homeostasis in obesity. 목 적 : 이번 연구는 성인 비만군에서 운동 전후 체중 감소와 관련하여 에너지 항상성 조절에 관여하는 것으로 알려진 혈장 ghrelin 농도의 변화가 있는지 알아보기 위한 것이다. 방 법 : 총 32명의 성인 여성을 대상으로 BMI 25 kg/ m2를 기준으로 18명의 정상 대조군과 14명의 비만군으로 구분하여 12주간의 체중 감량운동을 실시하였다. 각 운동 전후 체중, BMI, 체질량 지수, 체지방 측정을 포함한 신체 계측과 혈장 지질 농도 및 ghrelin의 농도를 측정하여 두 군에서의 각 측정치의 변화량을 비교하였다. 결 과 : 운동 전 비만군에서는 체중, BMI, 체지방률, WHR와 총 콜레스테롤이 대조군에 비해 유의하게 높았으며, 운동 전 혈장 ghrelin의 농도는 성인 비만군에서 정상 대조군에 비해 현저하게 감소되어 있었다. 운동 후 체중 감소와 관련하여 비만군과 대조군 모두에서 혈장 ghrelin 농도가 증가하였으며, 혈장 ghrelin의 평균 변화량은 대조군에 비해 비만군에서 유의하게 높았다. 그러나 두 군에서 운동 전후의 체중 감소량과 혈장 ghrelin 농도 간의 유의한 선형적인 상관관계는 없었으며, 전체 대상군에서 운동 전 혈장 ghrelin 농도는 체중, BMI, 체지방률, 총 콜레스테롤, 유리 지방산 농도와 유의한 음의 상관관계를 나타냈고, 운동 후 혈장 ghrelin 농도의 변화량은 BMI의 변화량과 유의한 음의 상관성이 있었다. 하지만 비만군에서 운동 후 혈장 ghrelin 농도의 변화량과 상관성 있는 어떤 신체계측치 및 생화학적 검사치는 없었다. 결 론 : 이번 연구에서 비만 성인에서의 운동 전 혈장 ghrelin 농도는 정상 대조군에 비해 유의하게 감소되어 있었고, 운동 후에는 체중 감소와 관련하여 비만군에서 대조군에 비해 더 많은 혈장 ghrelin 농도의 증가가 있었으며 이는 ghrelin이 체중 감소에 따른 보상반응으로 에너지 항상성을 유지하려는 기전에 의한 것으로 사료된다.

Multiple signaling pathways mediate ghrelin-induced proliferation of hippocampal neural stem cells

Chung, Hyunju,Li, Endan,Kim, Yumi,Kim, Sehee,Park, Seungjoon Society for Endocrinology 2013 The Journal of endocrinology Vol.218 No.1

<P>Ghrelin, an endogenous ligand for the GH secretagogue receptor (GHS-R) receptor 1a (GHS-R1a), has been implicated in several physiologic processes involving the hippocampus. The aim of this study was to investigate the molecular mechanisms of ghrelin-stimulated neurogenesis using cultured adult rat hippocampal neural stem cells (NSCs). The expression of GHS-R1a was detected in hippocampal NSCs, as assessed by western blot analysis and immunocytochemistry. Ghrelin treatment increased the proliferation of cultured hippocampal NSCs assessed by BrdU incorporation. The exposure of cells to the receptor-specific antagonist <SMALL>d</SMALL>-Lys-3-GHRP-6 abolished the proliferative effect of ghrelin. By contrast, ghrelin showed no significant effect on cell differentiation. The expression of GHS-R1a was significantly increased by ghrelin treatment. The analysis of signaling pathways showed that ghrelin caused rapid activation of ERK1/2 and Akt, which were blocked by the GHS-R1a antagonist. In addition, ghrelin stimulated the phosphorylation of Akt downstream effectors, such as glycogen synthase kinase (GSK)-3β, mammalian target of rapamycin (mTOR), and p70<SUP>S6K</SUP>. The activation of STAT3 was also caused by ghrelin treatment. Furthermore, pretreatment of cells with specific inhibitors of MEK/ERK1/2, phosphatidylinositol-3-kinase (PI3K)/Akt, mTOR, and Jak2/STAT3 attenuated ghrelin-induced cell proliferation. Taken together, our results support a role for ghrelin in adult hippocampal neurogenesis and suggest the involvement of the ERK1/2, PI3K/Akt, and STAT3 signaling pathways in the mediation of the actions of ghrelin on neurogenesis. Our data also suggest that PI3K/Akt-mediated inactivation of GSK-3β and activation of mTOR/p70<SUP>S6K</SUP> contribute to the proliferative effect of ghrelin.</P>

백서에서 성장호르몬과 그렐린의 상호작용에 관한 연구

이성용,양세원,신충호 대한소아내분비학회 2009 Annals of Pediatirc Endocrinology & Metabolism Vol.14 No.2

Purpose:The aim of this study was to determine whether there is a feedback relationship between pituitary growth hormone (GH) and gastric ghrelin. Methods:We intravenously administered 10 µg of either rat ghrelin or normal saline to adult male Sprague-Dawley rats and then measured the plasma GH levels and the mRNA expression levels of pituitary GH mRNA and hypothalamic GH-releasing hormone (GHRH) mRNA. Human GH (500 μg/kg, twice a day) or normal saline was subcutaneously administered to rats with or without food for 3 days. Thereafter, the plasma ghrelin levels and the ghrelin mRNA levels in the stomach were measured. Results:The plasma GH levels increased more significantly in rats that were administered ghrelin than in controls (P˂0.05). The mRNA levels of pituitary GH and hypothalamic GHRH were similar in the 2 groups. The plasma ghrelin levels and the stomach ghrelin mRNA levels were not affected by GH administration. Fasting significantly increased plasma ghrelin levels (P˂0.05) and stomach ghrelin mRNA levels (P˂0.05). Conclusion:Exogenous ghrelin administration only stimulated GH secretion without stimulating the synthesis of GH and GHRH. The synthesis and secretion of ghrelin were not suppressed by exogenous GH administration. These findings indicate that there is no feedback relationship between pituitary GH and gastric ghrelin. 목 적:본 연구에서 성장호르몬과 그렐린의 상호작용에 의해 서로의 합성과 혈중 농도에 미치는 영향에 대해 살펴보고자 하였다. 방 법:수컷 Sprague-Dawley 쥐(체중 250-300 g)를 대상으로 쥐 그렐린 10 μg 혹은 동량의 생리식염수를 정맥주사한 후 10분 뒤 혈장 성장호르몬 농도를 측정하고 즉시 단두하여 뇌하수체의 성장호르몬 mRNA와 시상하부의 성장호르몬방출호르몬 mRNA의 발현을 측정하였다. 또 식이를 제한하지 않은 군과 금식시킨 군으로 나누어 3일간 사람 성장호르몬 500 μg/kg 또는 동량의 생리식염수를 하루 2번 피하주사 한 후 혈장 그렐린 농도와 위의 그렐린 mRNA의 발현을 측정하였다. 결 과:혈장 성장호르몬은 그렐린을 투여한 군에서 식염수를 투여한 군보다 유의하게 높았다(P˂0.05). 그러나 뇌하수체의 성장호르몬 mRNA와 시상하부의 성장호르몬방출호르몬 mRNA의 발현은 두 군 간에 차이가 없었다. 금식 여부에 관계없이 3일간 성장호르몬을 투여한 군의 혈장 그렐린 농도와 위의 그렐린 mRNA의 발현은 식염수를 투여한 군과 유의한 차이가 없었다. 금식 여부에 따른 비교를 하였을 때, 금식을 시킨 군에서 혈장 그렐린 농도(P˂0.05)와 위의 그렐린 mRNA 발현(P˂0.05)은 유의하게 증가하였고 결 론:그렐린의 투여는 성장호르몬의 분비를 촉진시키나 성장호르몬 및 성장호르몬방출호르몬의 생성을 증가시키지는 않는다. 또 위의 그렐린 생성과 혈장 그렐린 농도는 성장호르몬 투여의 영향을 받지 않아 음성 되먹이기 기전이 존재하지 않는 것으로 보인다.

Ghrelin 유전자의 Leu72Met 다형성 분석에서 PCR-RFLP, PCR-SSCP, Amplication Refractory Mutation System(ARMS)의 비교분석

강주성,김세림,김선영,주찬웅,조수철,황평한,Kang, Ju Sung,Kim, Se Rim,Kim, Sun Young,Joo, Chan Uhng,Cho, Soo Chul,Hwang, Pyoung Han 대한소아청소년과학회 2005 Clinical and Experimental Pediatrics (CEP) Vol.48 No.10

목 적 : 성장호르몬 분비를 촉진하는 ghrelin는 여러 질병에서의 역할은 아직까지 잘 알려져 있지 않았다. 그러나 최근에 ghrelin 유전자 변이가 비만과 당뇨병과 관련이 있는 것으로 알려졌다. 현재까지 보고된 ghrelin 유전자 이상으로는 SNP인 Arg51Gln, Leu72Met, G274A가 있으며 이중 가장 흔한 이상인 Leu72Met 변이이다. 일반적으로 ghrelin 유전자의 Leu72Met와 같은 diallelic 다형성을 스크리닝하는데 SSCP, RFLP, sequencing 등이 사용되어 왔으나 향후 비만 환자들에서 가장 효과적이고 정확하게, 손쉽게 ghrelin 유전자의 Leu72Met 다형성 분석을 검출할 수 있는 스크리닝 방법을 찾아 임상적 적용에 이용하고자 하였다. 방 법 : 비만소아에서 ghrelin 유전자의 Leu72Met 다형성 분석을 PCR-RFLP, PCR-SSCP와 ARMS 분석 방법을 이용하여 비교분석하고 이들의 검사방법의 장단점을 알아보았다. 결 과 : PCR-RFLP, PCR-SSCP와 ARMS 분석 모두에서 allele 특이산물의 밴드가 뚜렷이 구별할 수 있었으며 상기 방법에 의한 결과는 모두에서 일치하였다. PCR-SSCP 방법은 점돌연변이의 존재 여부를 많은 시료를 대상으로 쉽게 분자학적 스크리닝할 수 있는 장점이 있으나 조작이 간단하지 않고 비용부담이 많다. BsrI 제한효소를 이용한 PCR-RFLP법은 비교적 용이하고 간단하여 널리 쓰이는 방법이지만 충분한 고농도의 DNA가 필요하며 전기영동 결과의 올바른 해석이 쉽지 않았다. 이에 비하여 ARMS 분석법은 위의 방법들보다는 간편하여 검사의 소요시간도 짧으며, 검출률이 높고 결과 해석이 매우 쉬웠다. 결 론 : 따라서 본 실험에서 시행한 ghrelin의 Leu72Met 유전자의 다형성을 결정하는 방법 중에는 ARMS 분석법이 정확하고 검사 분석법 및 결과 해석이 매우 쉽고 검사의 소요시간도 짧아 대량 검체에 적용에 매우 효과적으로 사료된다. 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.

Metabolic Syndrome is Associated with Lower Plasma Levels of Desacyl Ghrelin and Total Ghrelin in Asymptomatic Middle-aged Korean Men

조영혜,이상엽,정동욱,조아라,전정숙,김윤진,이정규,이유현,탁영진,황혜림,이승훈,이선민 대한비만학회 2017 The Korean journal of obesity Vol.26 No.2

Background: Desacyl ghrelin is acylated by ghrelin O-acyltransferase (GOAT) and converted to acyl ghrelin. To date, little is known about the relationship among the levels of these two forms of ghrelin, GOAT level, and insulin resistance in Asian individuals. The purpose of this study was to determine the relationship between insulin resistance and the levels of plasma acyl ghrelin, desacyl ghrelin, and GOAT in asymptomatic middle-aged Korean men. Methods: This cross-sectional study evaluated 78 asymptomatic middle-aged Korean men with metabolic syndrome (MS). We examined the correlation between the plasma levels of acyl ghrelin, desacyl ghrelin, and GOAT and sociodemographic, dietary, anthropometric, and metabolic parameters, as well as the association between insulin resistance and plasma levels of acyl ghrelin, desacyl ghrelin, and GOAT. Results: The levels of desacyl ghrelin and total ghrelin were significantly lower in the MS group than in the non-MS group (P<0.017, P=0.01, respectively). HOMA-IR values showed a significant negative correlation with desacyl ghrelin (r=–0.271, P=0.017) and total ghrelin (r=–0.271, P=0.016) levels. Acyl ghrelin and GOAT were not significantly correlated with HOMA-IR, and no correlation was found between the plasma levels of the two ghrelin types and GOAT. Conclusion: The plasma levels of desacyl ghrelin and total ghrelin in middle-aged Korean men with MS were lower than in those without MS. A significant negative correlation was observed between desacyl ghrelin level and HOMA-IR; however, no correlation was found between plasma levels of acyl ghrelin and GOAT and HOMA-IR.

The Effects of Exercise-induced Weight Loss on Ratio of Acylated and Unacylated Ghrelin in Obese Adolescents

Tae-Gil Yang,Hyun-Jun Kim(김현준),Goon-Soo Shin 한국생활환경학회 2013 한국생활환경학회지 Vol.20 No.2

본 연구는 신체구성, 혈중지질, adiponectin, total ghrelin, acylated ghrelin 비율, unacylated ghrelin 비율에 미치는 운동효과에 대해 알아보고자 20명의 비만 청소년을 대상으로 운동군 10명, 대조군 10명으로 무선표집하여, 유산소운동과 저항운동이 포함된 12주 복합운동을 실시하였다. 복합운동프로그램은 주 3회 55-64%와 65-75% 강도로 실시하였다. 모든 변인은 복합운동 프로그램 전·후 2회 측정하였으며, 신체구성, 혈중지질, adiponectin, total ghrelin, acylated ghrelin을 측정했다. 연구 수행 결과 체중 weight (p = 0.002), BMI(p = 0.04), body fat percentage(p = 0.03), body fat mass(p=0.008), lean body mass percentage(p = 0.039), TC(p = 0.032), LDL-C(p = 0.039), total ghrelin(p = 0.004), unacylated ghrelin(p = 0.003), acylated ghrelin 비율(p < 0.001), unacylated ghrelin 비율(p < 0.001)이 집단간 유의한 차이를 보이며 변한 것으로 나타났다. 결론적으로 12주 복합운동이 total ghrelin에서의 acylated ghrelin 비율을 낮추고 unacylated ghrelin을 증가시키는 것을 볼 때 지속적인 운동프로그램 참여로 비만 청소년의 식욕과 에너지대사가 개선됨을 알 수 있다. The purpose of this study is to determine the effect of combined exercise on ratio of acylated and unacylated ghrelin during a 12-week aerobic and resistant training program in untrained obese adolescent. Twenty 13-year-old boys were randomly assigned to one of two groups: a control group who performed no additional exercise and an exercise group who performed a combined exercise. The combined exercise program, consisting of aerobic exercise and resistance training, was performed by the experimental group under supervision for 12-week(three times a week) at 55-64% and 65- 75% of maximum. At baseline and 12 weeks, body composition, lipid profile, total ghrelin and acylated ghrelin were measured. There were significant differences between the groups in the pattern of change of weight(p = 0.002), BMI(p = 0.04), body fat percentage(p = 0.03), body fat mass(p = 0.008), lean body mass percentage(p = 0.039), TC(p = 0.032), LDL-C(p = 0.039), total ghrelin(p = 0.004), unacylated ghrelin(p = 0.003), ratio of acylated ghrelin(p<0.001), and ratio of unacylated ghrelin(p < 0.001) levels during the 12-week study. These findings suggest that exercise ameliorate appetite and energy metabolism of obese adolescent through ratio of acylated ghrelin and unacylated ghrelin levels changing from 12-week combined exercise.