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Nat Commun:Tempol通过改变肠道微生物群降低肥胖

来源:Nature Communications 2013-10-15 09:33

2013年9月24日,Nature Communications上发表的一篇论文提出,抗氧化剂Tempol通过改变小肠微生物群来降低小鼠的肥胖。这项研究提出了肠道微生物群在药物作用和体重调控中都有所涉及的另一个例子,同时也揭示了小肠中一个可能会被证明是减肥药物有用目标的信号通道。

Frank Gonzalez及同事用Tempol对小鼠进行处理,并在小肠里的主要微生物群中检测到一个变化。这一变化导致在与牛磺酸共轭的胆汁酸降解中所涉及的一种微生物酶的活性降低,同时小肠中的胆汁酸水平在处理过程中相应提高。与牛磺酸共轭的胆汁酸已知会降低FXR信号作用,后者是在胆汁酸、脂质和葡萄糖代谢中所涉及的一个通道。虽然尚不清楚Tempol对人类肥胖或肠道微生物群是否会有任何效应,但这项研究为解释Tempol怎样影响小鼠的肥胖提供了一个可能的机制,同时也表明FXR信号作用通道可能是治疗代谢病的一个合适的目标。(生物谷Bioon.com)

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Nature Communications  doi:10.1038/ncomms3384

Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity

Fei Li,Changtao Jiang,Kristopher W. Krausz,Yunfei Li,Istvan Albert,Haiping Hao,Kristin M. Fabre,James B. Mitchell,Andrew D. Patterson& Frank J. Gonzalez 
 
The antioxidant tempol reduces obesity in mice. Here we show that tempol alters the gut microbiome by preferentially reducing the genus Lactobacillus 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 FxrΔIE mice, 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.

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