The gut microbiota as an environmental factor that regulates fat storage
The gut microbiota as an environmental factor that regulates fat storage
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DOI：
10.1073/pnas.0407076101
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发表时间：
2004-11-02
影响因子：
11.1
通讯作者：
Gordon, JI
中科院分区：
文献类型：
--
作者：
Bäckhed, F;Ding, H;Gordon, JI
考虑到肥胖症在全球范围内的流行，新的治疗靶点对能量摄入、吸收或储存的非认知减少至关重要。肠道微生物群落（微生物群）对于加工膳食多糖至关重要。我们发现，尽管减少了食物摄入量，但从传统饲养动物的远端肠道（盲肠）采集正常微生物群的成年无菌（GF）C57 BL/6小鼠的常规化在14天内使体脂含量和胰岛素抵抗增加了60%。对GF和常规小鼠的研究表明，微生物群促进肠腔中单糖的吸收，从而诱导从头肝脂肪生成。禁食诱导的脂肪细胞因子（Fiaf），血管生成素样蛋白家族的成员，在正常小鼠的肠上皮中被选择性抑制。对GF和常规、正常和Fiaf敲除小鼠的分析确定，Fiaf是循环脂蛋白脂肪酶抑制剂，并且其抑制对于脂肪细胞中微生物诱导的甘油三酯沉积是必不可少的。对Rag 1（-/-）动物的研究表明，这些宿主反应不需要成熟的淋巴细胞。我们的研究结果表明，肠道微生物群是一个重要的环境因素，影响宿主从饮食和能量储存中获得能量。
New therapeutic targets for noncognitive reductions in energy intake, absorption, or storage are crucial given the worldwide epidemic of obesity. The gut microbial community (microbiota) is essential for processing dietary polysaccharides. We found that conventionalization of adult germ-free (GF) C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. Studies of GF and conventionalized mice revealed that the microbiota promotes absorption of monosaccharides from the gut lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is selectively suppressed in the intestinal epithelium of normal mice by conventionalization. Analysis of GF and conventionalized, normal and Fiaf knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor and that its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. Studies of Rag1(-/-) animals indicate that these host responses do not require mature lymphocytes. Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host.