2013年9月24日，Nature Communications上發(fā)表的一篇論文提出,，抗氧化劑Tempol通過改變小腸微生物群來降低小鼠的肥胖。這項(xiàng)研究提出了腸道微生物群在藥物作用和體重調(diào)控中都有所涉及的另一個(gè)例子,，同時(shí)也揭示了小腸中一個(gè)可能會(huì)被證明是減肥藥物有用目標(biāo)的信號(hào)通道,。
Frank Gonzalez及同事用Tempol對(duì)小鼠進(jìn)行處理,，并在小腸里的主要微生物群中檢測(cè)到一個(gè)變化。這一變化導(dǎo)致在與?；撬峁曹椀哪懼峤到庵兴婕暗囊环N微生物酶的活性降低,，同時(shí)小腸中的膽汁酸水平在處理過程中相應(yīng)提高。與?；撬峁曹椀哪懼嵋阎獣?huì)降低FXR信號(hào)作用,，后者是在膽汁酸、脂質(zhì)和葡萄糖代謝中所涉及的一個(gè)通道,。雖然尚不清楚Tempol對(duì)人類肥胖或腸道微生物群是否會(huì)有任何效應(yīng),，但這項(xiàng)研究為解釋Tempol怎樣影響小鼠的肥胖提供了一個(gè)可能的機(jī)制，同時(shí)也表明FXR信號(hào)作用通道可能是治療代謝病的一個(gè)合適的目標(biāo),。(生物谷Bioon.com）
生物谷推薦的英文摘要
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.
