Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue.

Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue.
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DOI:
10.3389/fmicb.2011.00149
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发表时间:
2011
影响因子:
5.2
通讯作者:
Cani PD
Cani PD
中科院分区:
生物学2区
文献类型:
--
作者:
Geurts L;Lazarevic V;Derrien M;Everard A;Van Roye M;Knauf C;Valet P;Girard M;Muccioli GG;François P;de Vos WM;Schrenzel J;Delzenne NM;Cani PD

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越来越多的证据支持肠道微生物群在肥胖、2型糖尿病和低度炎症发展中的作用。已发现脂肪组织的内分泌活动有助于葡萄糖稳态和低度炎症的调节。在该组织产生的关键激素中,爱帕琳已被证明可以调节葡萄糖稳态。最近,已经提出肠道微生物群通过内源性大麻素系统(eCB)和肠道微生物群衍生的化合物,即脂多糖(LPS)参与脂肪组织代谢。我们通过焦磷酸测序和16 S核糖体RNA基因序列的系统发育微阵列分析,研究了肥胖和糖尿病瘦素耐药小鼠(db/db)的肠道微生物群组成。我们观察到与瘦小鼠相比,db/db小鼠中厚壁菌门、变形菌门和纤维杆菌门的丰度显著更高。10个属的丰度受基因型影响显著。我们确定了eCB和LPS在遗传性肥胖和糖尿病小鼠中apelin能系统张力(apelin和APJ mRNA表达)的调节中的作用。通过使用体内和体外模型,我们已经证明了eCB和低度炎症差异调节脂肪组织中的apelin和APJ mRNA表达。最后,深肠道微生物群分析显示,2型糖尿病小鼠的肠道微生物群落与其瘦小鼠的肠道微生物群落显著不同。这表明肠道微生物群和apelinergic系统的调节之间的特定关系。然而,特定细菌在形成db/db小鼠表型中的确切作用仍有待确定。
Growing evidence supports the role of gut microbiota in the development of obesity, type 2 diabetes, and low-grade inflammation. The endocrine activity of adipose tissue has been found to contribute to the regulation of glucose homeostasis and low-grade inflammation. Among the key hormones produced by this tissue, apelin has been shown to regulate glucose homeostasis. Recently, it has been proposed that gut microbiota participate in adipose tissue metabolism via the endocannabinoid system (eCB) and gut microbiota-derived compounds, namely lipopolysaccharide (LPS). We have investigated gut microbiota composition in obese and diabetic leptin-resistant mice (db/db) by combining pyrosequencing and phylogenetic microarray analysis of 16S ribosomal RNA gene sequences. We observed a significant higher abundance of Firmicutes, Proteobacteria, and Fibrobacteres phyla in db/db mice compared to lean mice. The abundance of 10 genera was significantly affected by the genotype. We identified the roles of the eCB and LPS in the regulation of apelinergic system tone (apelin and APJ mRNA expression) in genetic obese and diabetic mice. By using in vivo and in vitro models, we have demonstrated that both the eCB and low-grade inflammation differentially regulate apelin and APJ mRNA expression in adipose tissue. Finally, deep-gut microbiota profiling revealed that the gut microbial community of type 2 diabetic mice is significantly different from that of their lean counterparts. This indicates specific relationships between the gut microbiota and the regulation of the apelinergic system. However, the exact roles of specific bacteria in shaping the phenotype of db/db mice remain to be determined.
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