減重影響細胞激素之統合分析及基因與減重對於細胞激素的影響

A meta-analysis of weight loss on cytokines and the effects of gene and weight loss on cytokines

涂瑜君(Yu-Chun Tu)

指導教授 ： 王姿乃

高雄醫學大學/健康科學院/公共衛生學研究所/碩士(2009年)

摘要

前言：近幾十年來，人類肥胖的盛行率節節高升。所謂肥胖，是指異常或過度的脂肪組織堆積，或由於熱量攝入的速率遠遠超過消耗的速率因而導致體重增加，並且損害身體健康。肥胖的原因被認為是涉及基因、環境和其他因素的複雜疾病。而一些細胞激素(CRP、ghrelin、leptin、TNF-α、IL-6、adiponectin)被認為，是會造成肥胖引起許多疾病的因子之一。
研究目的：本研究欲探討肥胖者與非肥胖者之間細胞激素的差異，並且偵測減重介入前後，肥胖者細胞激素的差異，及其與三種單核苷酸多型性(SNP)的關係。並且用統合性分析探討減重介入對於細胞激素的效果為何。
材料與方法：本研究之統合性分析，從PubMed, MEDLINE, Cochrane Library 等資料庫搜尋文獻，以嚴格的納入及排除標準排除386篇文獻。探討運動及飲食減重方式介入或orlistat減重藥物介入對於細胞激素(CRP、TNF-α、IL-6、adiponectin)的影響，19篇文獻皆為隨機控制試驗設計之文獻。
另外，本研究之減重介入研究，募集35位肥胖者(BMI≧25)以及35位年齡、性別配對的非肥胖者(BMI＜25)。研究進行減重介入2~3個月，減重前後皆測量體位資料以及採集血液。血液用來分析生化值、細胞激素濃度，以及萃取DNA以作基因型別定序。三種單核苷酸多型性(SNP)為Leptin SNP (-2548 A/G, rs7799039)、Ghrelin SNP (Leu72Met, rs696217)、CRP SNP(+1059 G/C, rs1800947)。
結果：本研究統合分析19篇隨機控制試驗設計文獻之結果，減重後CRP、IL-6以及TNF-α濃度有顯著的下降，且adiponectin濃度是顯著上升。並且運動飲食介入組的改善比上orlistat減重藥物介入組較為明顯。
減重介入研究發現肥胖者的leptin、hs-CRP濃度都顯著比非肥胖組高；而ghrelin濃度則是肥胖組顯著的較低(p皆<0.001)。2~3個月減重後，leptin有顯著的下降，ghrelin是顯著的上升(p皆<0.01)。
Leptin SNP (-2548 A/G, rs7799039) AA型的個案三酸甘油脂和hs-CRP濃度較AG/GG型者高(p皆<0.05)。2~3個月減重介入後，Leptin SNP基因型在校正性別後，AA型的個案顯著降低較多的體脂肪率(p=0.01)、舒張壓(p=0.04)、膽固醇濃度(p=0.04)以及hs-CRP濃度(p=0.03)。
結論：本研究發現減重介入對於細胞激素的改善的確有影響，可見減重可以確實改善發炎狀態。並且研究結果指出，leptin基因型(-2548 A/G, rs7799039)可能和肥胖的狀態以及減重改善細胞激素的程度有所關聯。

關鍵字

減重 ； 基因 ； 統合分析 ； 細胞激素

並列摘要

Introduction：In recent decades, the prevalence of obesity is rising because people are eating and less active. Obesity is defined as abnormal or excessive fat accumulation that may impair health. Obesity is related to genetic, environmental and other factors. And some cytokines (CRP, ghrelin, leptin, TNF-α, IL-6, adiponectin) are thought to be factors that cause chronic diseases in obese subjects.
Objective：Our study objective was to determine the differences of cytokine between obese and non-obese subjects. We want to detect cytokine change during weight loss intervention, and to evaluate the relationship between the changes of cytokines and three SNPs. Furthermore, meta-analysis was used to evaluate the effect of weight loss on cytokines.
Materials and Methods：In this weight control study, we recruited 35 obese subjects (BMI ≧ 25) as well as 35 age and sex-matched non-obese subjects (BMI < 25) and performed an intervention study of weight control for 2 ~ 3 months. All subjects were measured anthropometric data and blood samples were collected before and after weight control intervention. We analyzed the biochemical values and cytokine concentrations, as well as the extraction of DNA for genotyping. We selected three SNPs which are leptin (-2548 A/G, rs7799039)、ghrelin (Leu72Met, rs696217)、CRP(+1059 G/C, rs1800947) genes. In our meta-analysis, we reviewed the literature from PubMed, MEDLINE, Cochrane Library database, with strict inclusion and exclusion criteria to exclude 386 papers. We want to explore the relationships of intervention of exercise/diet or orlistat medication drugs with cytokines (CRP, TNF-α, IL-6, adiponectin) improvement in 19 papers. All papers were randomized and controlled for intervention study.
Results：We found that leptin, hs-CRP concentrations in obese subjects are significantly higher than non-obese subjects, and ghrelin is significantly lower in obese subjects than non-obese subjects (p all <0.001). After weight loss, we found a significant declined in leptin and increased in ghrelin (p all <0.01). Leptin SNP (-2548 A/G, rs7799039) AA carriers have significantly higher triglyceride and hs-CRP concentrations than AG/GG carriers. After weight loss, AA carriers significantly reduce percentage body fat, diastolic blood pressure, cholesterol and hs-CRP concentrations than AG/GG carriers. Our meta-analysis included 19 papers, we found that CRP, IL-6, TNF-α were significantly reduced, and adiponectin increased after weight control. We provide evidence that improvements of cytokines in exercise/diet intervention group are significantly different from orlistat intervention group.
Conclusion：Our study indicated that weight control intervention can indeed improve cytokines and show that weight loss can modify the inflammatory state. And we suggested that leptin SNP (-2548 A/G, rs7799039) can partly influence obesity and the effect on weight loss.

並列關鍵字

weight reduction ； SNP ； meta-analysis ； cytokine

參考文獻

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