Abstract
Increasing studies have shown that obesity is the primary cause of cardiovascular diseases, non-alcoholic fatty liver diseases, type 2 diabetes, and a variety of cancers. The dysfunction of gut microbiota was proved to result in obesity. Recent research indicated ANGPTL4 was a key regulator in lipid metabolism and a circulating medium for gut microbiota and fat deposition. The present study was conducted to investigate the alteration of gut microbiota and ANGPTL4 expression in the gastrointestinal tract of mice treated by the high-fat diet. Ten C57BL/6J mice were randomly allocated to two groups and fed with a high-fat diet (HFD) containing 60% fat or a normal-fat diet (Control) containing 10% fat. The segments of ileum and colon were collected for the determination of ANGPTL4 expression by RT-qPCR and immunohistochemical analysis while the ileal and colonic contents were collected for 16S rRNA gene sequencing. The results showed HFD significantly increased mice body weight, epididymal fat weight, perirenal fat weight, liver weight, and the lipid content in the liver (P < 0.05). The relative expression of ANGPTL4 and the ANGPTL4-positive cells in the ileum and colon of mice was significantly increased by HFD treatment. Furthermore, 16S rRNA gene sequencing of the ileal and colonic microbiota suggested that HFD treatment changed the composition of the gut microbiota. The ratio of Firmicutes to Bacteroidetes and the abundance of Allobaculum was significantly higher in the HFD group than in the Control group while the abundance of Adlercreutzia, Bifidobacterium, Prevotellaceae UCG-001, and Ruminococcus was significantly decreased. Interestingly, the abundance of Allobaculum was positively correlated with the expression of ANGPTL4. These findings provide a theoretical foundation for the development of strategies to control the obesity and related diseases by the regulation of ANGPTL4 and gut microbiota.
Highlights
The epidemic rise in obesity has chronically challenged human health, performance and quality of life with affecting more than 2 billion people in the world and being related to diabetes, cancers and cardiovascular diseases [1, 2]
This study found that the body weight of the mice was increased by 82.31% (P < 0.05) with the high-fat diet (HFD) treatment
Studies revealed that the abundance of Allobaculum might be negatively correlated with inflammation, insulin resistance and obesity with the intervention of ginger [59], berberine and metformin [60], or prebiotics [61] in mice. Consistent with these studies, our results found the significant increase in the relative abundance of Allobaculum and the expression level of ANGPTL4 by the HFD treatment in mice
Summary
The epidemic rise in obesity has chronically challenged human health, performance and quality of life with affecting more than 2 billion people in the world and being related to diabetes, cancers and cardiovascular diseases [1, 2]. Increasing evidences indicate that gut microbiota directly participates in obesity and many other metabolic diseases [4, 5]. The dysregulation in the composition and metabolic functions of gut microbiota would promote the development of obesity [7]. The microbiota transplantation from girls with or without obesity to mice showed a close relationship between gut microbiota and obesity [8]. Gut microbiota is closely related to host lipid metabolism, the disorder of which alters the composition of gut microbiota. The dysfunctional gut microbiota would further affects the host lipid metabolism in turn [10]
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