Abstract

Introduction Accumulating evidence has indicated that alterations of gut microbiota have been involved in various metabolic diseases. Orlistat, a reversible inhibitor of pancreatic and gastric lipase, has beneficial effects on weight loss and metabolism. However, the effect of orlistat on the composition of gut microbiota remains unclear. Objective We aimed to explore the effect of orlistat on gut microbiota in high-fat diet (HFD) fed C57BL/6J obese mice. Methods C57BL/6J mice were randomly divided into three groups: control (NCD), HFD, and HFD + orlistat (ORL). Mice in the NCD group were fed chow diet, while the other groups were fed HFD for 6 months, and orlistat was added in the final 3 months in the HFD + ORL group. After sacrifice, body weight and metabolic parameters were assessed, and the gut microbial composition was analyzed by 16S rRNA gene sequencing. Results Orlistat treatment exerted beneficial effects on body weight, plasma cholesterol, and glucose tolerance. Meanwhile, orlistat treatment modified the gut microbiota, presenting as reduced total microbial abundance and obvious upregulated bacteria. Moreover, the upregulated bacteria correlated with several metabolic pathways. Conclusions Orlistat may exert beneficial effects on body weight and glucose tolerance through modifying the composition of gut microbiota.

Highlights

  • Accumulating evidence has indicated that alterations of gut microbiota have been involved in various metabolic diseases

  • The other three studies documented the efficacy of orlistat on glucose improvements and possible biochemical conversion to type 2 diabetes [21, 23, 24]

  • Chronic high-fat diet (HFD) consumption resulted in weight gain and impaired glucose tolerance, whereas treatment with orlistat decreased body weight significantly and improved the glucose tolerance than mice in HFD group

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Summary

Introduction

Accumulating evidence has indicated that alterations of gut microbiota have been involved in various metabolic diseases. We aimed to explore the effect of orlistat on gut microbiota in high-fat diet (HFD) fed C57BL/6J obese mice. Orlistat treatment exerted beneficial effects on body weight, plasma cholesterol, and glucose tolerance. Orlistat treatment modified the gut microbiota, presenting as reduced total microbial abundance and obvious upregulated bacteria. Orlistat may exert beneficial effects on body weight and glucose tolerance through modifying the composition of gut microbiota. Expanding evidence has shown that gut microbiota, as a key environmental factor, was involved in the development of obesity and metabolic disorders. Proposed mechanisms accounting for the causative link involve the roles of gut microbiota in elevation in energy production from diet [12], modulation of host metabolism [13], and contribution to chronic low-grade inflammation [14]

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