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研究成果

发现通过调节肠内菌群能抑制肠道FXR受体并有望治疗肥胖的研究成果

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    2013年12月2日,中国科学网一篇名为《调节肠内菌群有望治疗肥胖》的文章,报道了课题组最新的研究成果,除此之外,ScienceDailyGEN也都对该文章纷纷进行了报道。   

    通过研究,研究组观察到抗氧化药物Tempol能够降低高脂饮食诱导的小鼠体重。研究结果显示,tempol改变了肠道微生物,首先通过降低乳酸杆菌及其胆汁盐水解酶(BSH)并导致肠道牛黄β鼠胆酸的浓度增加,进而抑制了肠道参与体内脂肪和血糖代谢的法尼醇X受体(FXR)水平。 
    NIH癌症研究所代谢实验室主任Frank Gonzalez认为,抑制肠道FXR信号通道可能成为治疗肥胖药物的新靶点。

Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity
Abstract
The antioxidant tempol reduces obesity in mice. Here we show that tempol alters the gut microbiome by preferentially reducing the genusLactobacillus and its bile salt hydrolase (BSH) activity leading to the accumulation of intestinal tauro-β-muricholic acid (T-β-MCA). T-β-MCA is an farnesoid X receptor (FXR) nuclear receptor antagonist, which is involved in the regulation of bile acid, lipid and glucose metabolism. Its increased levels during tempol treatment inhibit FXR signalling in the intestine. High-fat diet-fed intestine-specific Fxr-null (FxrΔIE) mice show lower diet-induced obesity, similar to tempol-treated wild-type mice. Further, tempol treatment does not decrease weight gain in FxrΔIEmice, suggesting that the intestinal FXR mediates the anti-obesity effects of tempol. These studies demonstrate a biochemical link between the microbiome, nuclear receptor signalling and metabolic disorders, and suggest that inhibition of FXR in the intestine could be a target for anti-obesity drugs.

 


文章链接:
F. Li, C. Jiang, A.D. Patterson, K.W. Krausz, I. Albert, H. Hao, K.M. Fabre, J.B. Mitchell, A.D. Patterson, and F.J. Gonzalez. Microbiome remodeling leads to inhibition of intestinal farnesoid X receptor signaling and decreased obesity. Nature Communications 4: 2384 (2013).


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