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비만 청소년에서 혈장 Ghrelin, Acylghrelin 및 Obestatin 변동과 비만지표들의 성별 관련성

  • 엄지현 (대학원 의학과 약리학전공)

초록/요약

Ghrelin and obestatin are encoded by the ghrelin gene, and des-Gln14-ghrelin is produced by alternative splicing of the same gene. Both of ghrelin have the same potency as a GH secretogogue, but ghrelin would be transformed to acyl-ghrelin, the only peripheral orexigenic and adipogenic hormone, through a unique O-n-octanoylation at serine 3 by of ghrelin O-acyltransferase (GOAT). However, plasma des-Gln14-ghrelin/acy-lghrelin ration ranges from 2.5:1 to 9:1 in different studies, and des-acyl ghrelin was secreted in a highly regulated manner in a recent study on response of mice to food deprivation. Obestatin, unlike these ghrelins that are ligands to secretagogue receptor 1a (GHS-R1a), binds to a G protein-coupled receptor (GPR39, an orphan receptor belonging to the ghrelin receptor family) and was originally reported to inhibit food intkake, but the anorexigenic activity of obestatin remains debatable. Nevertheless, in a studies on human obesity (Guo et al., 2007), both preprandial plasma ghrelin and obestatin levels were lower in the obese compared with normal-weight controls, but the preprandial ghrelin/obestatin ratio was higher in the obese compared with normal weight controls, and the postprandial ghrelin/obestatin ratio was decreased both in the obese and controls compared with their preprandial levels, suggesting that the ghrelin&#8260;obestatin balance could play an essential part of the adaptation to nutritional challenges. Reinehr et al. (2008) reported that plasma obestatin and leptin levels were significantly higher and ghrelin concentrations were significantly lower in obese children compared to nonobese children, and that sustaining weight loss in obese children led to a significant increase in obestatin and to a significant decrease in leptin and insulin levels, while ghrelin level did not change. On the other hand, Vicennati et al. (2007) revealed that obese women had higher obestatin and lower ghrelin blood levels, and a lower ghrelin/obestatin ratio compared with controls, but in obese women, the ghrelin/obestatin ratio did not show correlation with any one of metabolic parameters, such as BMI, waist-to-hip ratio, fasting insulin, and HOMA-IR. In a recent study on childhood obesity, Pacifico et al. (2009) reported that plasma insulin and HOMA-IR were associated negatively with plasma total ghrelin and nonacylated ghrelin, but positively with the ghrelin and nonacylated ghrelin ratio, and that excess acyl-ghrelin may negatively modulate insulin action in obese and nonobese children, and may contribute to the association of insulin resistance and metabolic syndrome. Therefore, this study was designed in the aspect of gender difference of adolescent obesity in 13 obese Korean adolescents ( 6 males and 7 females ; mean age, 13.19 ± 2.20 years) and 37 nonobese Korean adolescents ( 17 males and 20 females ; mean age, 13.88 ± 2.37 years), to investigate the biological meaning of plasma total ghrelin, acyghrelin and obestatin levels and the concentration ratios among them by studying their correlations with metabolic parameters, such as insulin, leptin, and adiponectin levels in plasma and HOMA-IR values as well as BMI and hip-waist ratio. Plasma leptin level was significantly higher (p<0.01), plasma adiponectin level was somewhat lower (p<0.12) and the plasma leptin/adiponectin ratio was greater (P<0.02) in obese group compared to nonobese group. Plasma leptin/adiponectin ratio was significantly and positively correlated with BMI (r=0.453, P=0.001) and HOMA-IR (r=0.352, P=0.012). Plasma total ghrelin (P<0.02) and obestatin (P<0.02) levels were significantly lower, acyl ghrelin (P<0.08) was somewhat lower, and plasma acyl ghrelin/obestatin (P<0.04) and total ghrelin/obestatin ratios (P<0.04) were greater in obese group compared to nonobese group. On the other hand, plasma total ghrelin/obestatin ratio (P<0.05) was significanly greater in female than in male, but plasma acyl ghrelin/obestatin ratio (P<0.05) was significanly greater in male than in female. Plasma total ghrelin and acyl ghrelin levels, respectively, were negatively correlated with BMI (r=-0.325, P=0.005; r=-0.425, P=0.001) and waist-hip ratio (r=-0.265, P=0.020; r=-0.325, P=0.005), but were little correlated with plasma leptin and adiponectin levels. Plasma obestatin level was somewhat negatively correlated with waist-hip ratio (r=-0.130, P=0.185). Plasma total ghrelin/obestatin ratio presented significantly positive correlations with BMI (r=0.234, P=0.105) and HOMA-IR (r=0.326,P=0.021), respectively, and were significantly greater in male (r=0.421, P=0.036; r=0.513, P=0.009) but not in female when considered separately. In addition, plasma acyl ghrelin/obestatin ratio presented significantly positive correlations with BMI (r=0.303, P=0.034) and HOMA-IR (r=0.331, P=0.019), respectively, and these correlations, respectively, were significantly greater in male (r=0.446, P=0.025; r=0.547, P=0.005) but not in female when considered separately. The results obtained in this study suggests that the imbalance of plasma ghrelin and obestatin levels - decrease in plasma ghrelin and obestatin levels and increase in plasma ghrelin to obestatin ratio - may be correlated with obesity in Korean adolescents, and that plasma acy-ghrelin to obestatin ratio may contribute to insulin resistance in obese male adolescents. Further extensive larger cohort studies should be needed to unravel the biological roles of ghrelin and obestatin and the gender different features in obese adolescents.

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목차

영문초록: Abstract
I. 서 론 1
II. 연구 대상 및 방법 20
III. 연구 성적 22
IV. 고 찰 25
V. 요 약 30
VI. 참고 문헌 33

성적 그림: Figures 55

성적 표: Tables 69

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