氧化基因變異 致肥元凶

氧化基因變異 致肥元凶

台灣研究首次發現與肥胖有關的氧化基因，冀助醫學界日後研發減肥的新方法。率領研究的台灣中央研究院院士李文華表示，當體內的氧化基因「NPGPx」出現變異，氧化壓力提升，體內脂肪便增加，今次發現有助破解為何有些人「食極唔肥」之謎。

抗氧化劑可抑制

研究團隊為證實氧化基因為致肥元凶，在動物實驗中，讓「NPGPx」基因變異的老鼠，服用含抗氧化劑的一種常用化痰藥物。結果顯示，老鼠服藥後，即使進食大量高脂肪食物，也不會肥胖，反映了服用抗氧化劑，有助對抗老鼠的肥胖問題。團隊稍後會進一步研發有關減肥藥，希望能為肥胖人士及相關慢性疾病，如糖尿病、高血壓等患者帶來新療法。今次研究結果刊登在國際期刊《歐洲分子生物組織分子醫學》。

不少天然蔬果都含有抗氧化劑，台灣營養師趙強表示，南瓜、菠菜、番茄、橙、葡萄，甚至中藥材如山藥、薏仁等都含抗氧化成份，市民多吃無妨。

本港中文大學內分泌科主管周振中表示，隨醫學界成功破解人類的基因圖譜，過去15至20年，一直積極進行基因研究工作，陸續發現多個基因與肥胖有關。主要涉及負責熱量平衡的基因，如控制飽肚感、熱量消耗等，但至今仍未成功研發出與基因有關的新療法，顯示治療人類肥胖研究的道路仍然漫長。

40%肥胖先天因素

台灣有關方面正計劃將抗氧化劑研發成減肥藥，令人食極唔肥。周振中認為，調控飲食才是減肥關鍵，市民不應誤解服用減肥藥後，便可肆無忌憚任食。他續稱，飲食自律很重要，港人常誤解「自己飲杯水都會肥」，從未真正了解自己的飲食餐單和生活習慣，其實大錯特錯。他們主要因進食量多於消耗量才會致肥，飲水本身不會令人肥胖。醫學界已知人類肥胖原因眾多，40%來自先天因素，包括遺傳基因，餘下60%為後天因素，包括飲食習慣、運動情況及生活環境等。

EMBO Mol Med. 2013 Aug;5(8):1165-79. doi: 10.1002/emmm.201302679. Epub 2013 Jul 4.

Deficiency of NPGPx, an oxidative stress sensor, leads to obesity in mice and human.

Chang YC, Yu YH, Shew JY, Lee WJ, Hwang JJ, Chen YH, Chen YR, Wei PC, Chuang LM, Lee WH.

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·         EMBO Mol Med. 2013 Aug;5(8):1147-8.

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Abstract

Elevated oxidative stress is closely associated with obesity. Emerging evidence shows that instead of being a consequence of obesity, oxidative stress may also contribute to fat formation. Nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) is a conserved oxidative stress sensor/transducer and deficiency of NPGPx causes accumulation of reactive oxygen species (ROS). In this communication, we show that NPGPx was highly expressed in preadipocytes of adipose tissue. Deficiency of NPGPx promoted preadipocytes to differentiate to adipocytes via ROS-dependent dimerization of protein kinase A regulatory subunits and activation of CCAAT/enhancer-binding protein beta (C/EBPβ). This enhanced adipogenesis was alleviated by antioxidant N-acetylcysteine (NAC). Consistently, NPGPx-deficient mice exhibited markedly increased fat mass and adipocyte hypertrophy, while treatment with NAC ablated these phenotypes. Furthermore, single nucleotide polymorphisms (SNPs) in human NPGPx gene, which correlated with lower NPGPx expression level in adipose tissue, were associated with higher body mass index (BMI) in several independent human populations. These results indicate that NPGPx protects against fat accumulation in mice and human via modulating ROS, and highlight the importance of targeting redox homeostasis in obesity management.

© 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.