Microbiota-induced obesity requires farnesoid X receptor.
Microbiota-induced obesity requires farnesoid X receptor.
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DOI：
10.1136/gutjnl-2015-310283
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发表时间：
2017-03
期刊：
影响因子：
24.5
通讯作者：
Bäckhed F
中科院分区：
文献类型：
--
作者：
Parséus A;Sommer N;Sommer F;Caesar R;Molinaro A;Ståhlman M;Greiner TU;Perkins R;Bäckhed F
肠道微生物群被认为是调节肥胖的环境因素，最近的证据表明，微生物群介导的胆汁酸谱变化和通过胆汁酸核受体法尼醇X受体（FXR）的信号传导有助于受损的宿主代谢。在这里，我们研究了肠道微生物群是否通过FXR调节肥胖和相关表型。我们给无菌（GF）和常规饲养（CONV-R）的野生型和Fxr−/−小鼠喂食高脂饮食（HFD）10周。 我们监测了体重增加和葡萄糖代谢，并分析了肠道微生物群和胆汁酸组成、β细胞质量、脂肪组织中巨噬细胞的积累、肝脏脂肪变性以及脂肪组织和肝脏中靶基因的表达。我们还将野生型和Fxr缺陷型小鼠的微生物群转移到GF野生型小鼠。肠道微生物群以FXR依赖的方式促进体重增加和肝脏脂肪变性，并且Fxr−/−和野生型小鼠之间的胆汁酸谱和粪便微生物群的组成不同。定殖野生型小鼠中的肥胖表型与增加的β细胞质量、增加的脂肪炎症、增加的脂肪变性和参与脂质摄取的基因表达相关。通过将HFD喂养的Fxr−/−和野生型小鼠的盲肠微生物群转移到GF小鼠中，我们表明肥胖表型是可转移的。我们的研究结果表明，肠道微生物群通过FXR促进饮食诱导的肥胖和相关表型，FXR可能通过改变微生物群组成而导致肥胖增加。
The gut microbiota has been implicated as an environmental factor that modulates obesity, and recent evidence suggests that microbiota-mediated changes in bile acid profiles and signalling through the bile acid nuclear receptor farnesoid X receptor (FXR) contribute to impaired host metabolism. Here we investigated if the gut microbiota modulates obesity and associated phenotypes through FXR. We fed germ-free (GF) and conventionally raised (CONV-R) wild-type and Fxr−/− mice a high-fat diet (HFD) for 10 weeks. We monitored weight gain and glucose metabolism and analysed the gut microbiota and bile acid composition, beta-cell mass, accumulation of macrophages in adipose tissue, liver steatosis, and expression of target genes in adipose tissue and liver. We also transferred the microbiota of wild-type and Fxr-deficient mice to GF wild-type mice. The gut microbiota promoted weight gain and hepatic steatosis in an FXR-dependent manner, and the bile acid profiles and composition of faecal microbiota differed between Fxr−/− and wild-type mice. The obese phenotype in colonised wild-type mice was associated with increased beta-cell mass, increased adipose inflammation, increased steatosis and expression of genes involved in lipid uptake. By transferring the caecal microbiota from HFD-fed Fxr−/− and wild-type mice into GF mice, we showed that the obesity phenotype was transferable. Our results indicate that the gut microbiota promotes diet-induced obesity and associated phenotypes through FXR, and that FXR may contribute to increased adiposity by altering the microbiota composition.
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影响因子：
8.7
作者：
Goudriaan, JR;Tacken, PJ;Jong, MC
通讯作者：
Jong, MC
DOI：
10.1073/pnas.0504978102
发表时间：
2005-08-02
影响因子：
11.1
作者：
Ley, RE;Bäckhed, F;Gordon, JI
通讯作者：
Gordon, JI
影响因子：
4.8
作者：
Kawamata, Y;Fujii, R;Fujino, M
通讯作者：
Fujino, M
DOI：
10.1016/s0006-291x(02)02550-0
发表时间：
2002-11-15
影响因子：
3.1
作者：
Maruyama, T;Miyamoto, Y;Tanaka, K
通讯作者：
Tanaka, K
影响因子：
15.9
作者：
Jiang, Changtao;Xie, Cen;Gonzalez, Frank J.
通讯作者：
Gonzalez, Frank J.