Gut microbiota mediates the anti-obesity effect of calorie restriction in mice.

Gut microbiota mediates the anti-obesity effect of calorie restriction in mice.
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DOI:
10.1038/s41598-018-31353-1
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发表时间:
2018-08-29
期刊:
影响因子:
4.6
通讯作者:
Chen Y
Chen Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang S;Huang M;You X;Zhao J;Chen L;Wang L;Luo Y;Chen Y

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热量限制(CR)延长了寿命,并在各种模式生物中产生了许多有益于健康和代谢的效应,但其潜在机制尚未完全了解。据报道,肠道微生物群与CR的有益作用相关;然而,尚不清楚CR的这些作用是否由肠道微生物群介导。在这项研究中,我们采用了一种由抗生素诱导的微生物耗尽的小鼠模型来研究肠道微生物群在CR中的功能作用。肠道微生物群的消耗使小鼠对CR诱导的体重减轻具有抵抗力,伴随着脂肪量的增加,瘦体重的减少和代谢率的下降。肠道微生物群的消耗导致空腹血糖和胆固醇水平升高,与CR无关。包括瘦素和胰岛素在内的一些代谢调节激素因CR和/或肠道微生物群耗竭而改变。此外,CR改变了肠道微生物群的组成,主要益生菌属如乳杆菌和双歧杆菌显著增加,螺杆菌减少。此外,我们在高脂饮食喂养的小鼠中进行了粪便微生物群移植。从热量限制小鼠转移微生物群的小鼠可以抵抗高脂饮食诱导的肥胖,并表现出代谢改善,例如减轻肝脏脂质积聚。总的来说,这些数据表明,CR诱导的代谢改善,特别是体重减轻,在一定程度上是由肠道微生物群介导的。
Calorie restriction (CR) extends lifespan and elicits numerous effects beneficial to health and metabolism in various model organisms, but the underlying mechanisms are not completely understood. Gut microbiota has been reported to be associated with the beneficial effects of CR; however, it is unknown whether these effects of CR are causally mediated by gut microbiota. In this study, we employed an antibiotic-induced microbiota-depleted mouse model to investigate the functional role of gut microbiota in CR. Depletion of gut microbiota rendered mice resistant to CR-induced loss of body weight, accompanied by the increase in fat mass, the reduction in lean mass and the decline in metabolic rate. Depletion of gut microbiota led to increases in fasting blood glucose and cholesterol levels independent of CR. A few metabolism-modulating hormones including leptin and insulin were altered by CR and/or gut microbiota depletion. In addition, CR altered the composition of gut microbiota with significant increases in major probiotic genera such as Lactobacillus and Bifidobacterium, together with the decrease of Helicobacter. In addition, we performed fecal microbiota transplantation in mice fed with high-fat diet. Mice with transferred microbiota from calorie-restricted mice resisted high fat diet-induced obesity and exhibited metabolic improvement such as alleviated hepatic lipid accumulation. Collectively, these data indicate that CR-induced metabolic improvement especially in body weight reduction is mediated by intestinal microbiota to a certain extent.
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