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肝臟中發現新型“肥胖因子”

文章來源:科技日報 楊雪 劉志偉   發布時間:2019-05-10  【字號:     】  

  近日,武漢大學生命科學學院宋保亮教授團隊發現,肝臟分泌的GPNMB蛋白,是一個新的“肥胖因子”,它通過上調脂肪組織的脂質合成基因、抑制機體產熱,最終引起肥胖及胰島素抵抗,而利用抗體中和血液GPNMB對肥胖和糖尿病有良好治療效果。

  近日,《自然》子刊《自然·代謝》在線發表了這項研究成果。同期雜志也發表預告對此進行了專題報道。論文題為《肝臟分泌的GPNMB蛋白促進白色脂肪組織脂質合成、加劇肥胖和胰島素抵抗》。

  根據世界衛生組織統計,2016年,18歲及以上的成年人中逾19億人超重,其中超過6.5億人肥胖。肥胖可受遺傳和環境等多因素影響,它不光影響體型,還是糖尿病、脂肪肝和心腦血管等疾病的重要危險因素。生命體作為一個有機整體,其脂質代謝過程除了在細胞內受到嚴格的調控之外,各個組織器官之間也存在多種形式的相互作用。

  宋保亮前期研究發現,在肝臟中特異敲除泛素連接酶gp78(L-gp78-/-)可導致SREBP通路抑制。有趣的是,研究人員發現在肝臟合成脂質能力下降的同時,脂肪組織脂質合成能力會代償性上調,這表明肝臟分泌某種“肥胖因子”,促進脂肪組織脂質合成。

  從這個現象出發,研究人員發現了肝臟分泌的GPNMB蛋白能顯著加重肥胖程度,增加脂肪組織脂質合成能力,抑制機體產熱,降低能量消耗,加重胰島素抵抗。而GPNMB中和抗體能有效逆轉肥胖小鼠的表型,減少脂肪組織重量,降低脂肪組織脂質合成基因的表達,促進脂肪組織產熱,并減輕胰島素抵抗。該研究成果表明,GPNMB就是一個新型“肥胖因子”,并證明靶向GPNMB可有效治療肥胖和糖尿病。




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