Abstract
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.
Highlights
Obesity and associated metabolic disorders are closely associated with a low-grade inflammatory state (Olefsky and Glass, 2010)
16S RRNA ANALYSIS OF GUT BACTERIAL POPULATIONS IN OBESE AND DIABETIC MICE COMPARED TO LEAN MICE Obese mice and diet-induced obese mice are characterized by an altered composition of the gut microbiota (Ley et al, 2005; Cani et al, 2007a,b; Turnbaugh et al, 2008, 2009)
Db/db mice become type 2 diabetic early after birth. This major difference between the two models confers to db/db mice a clear advantage for investigating the role of the gut microbiota in this phenotype
Summary
Obesity and associated metabolic disorders (e.g., insulin resistance, type 2 diabetes, and cardiovascular diseases) are closely associated with a low-grade inflammatory state (Olefsky and Glass, 2010). Compelling evidence supports the idea that adipokines participate in the regulation of glucose homeostasis and low-grade inflammation (Deng and Scherer, 2010; Federico et al, 2010). Among the recently discovered adipokines, apelin has been proposed as a novel key peptide involved in the regulation of several physiological functions. It has been proposed that inflammation could participate in the production of apelin and the modulation of its receptor expression (Daviaud et al, 2006; Han et al, 2008a,b).
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