Modulatory effect of gut microbiota on insulin sensitivity

Abstract

Gut microbiota is indispensable in regulating host metabolism. Current research focus on the role of gut microbiota in the progression of obesity, which is associated with numerous complications, including diabetes mellitus and cardiovascular diseases. The global prevalence of diabetes mellitus dramatically escalate in modern society. Altered gut microbiota has been identified in type 2 diabetic patients, suggesting gut microbiota may be involved in the development of type 2 diabetes mellitus. Furthermore, animal studies have demonstrated that gut microbial species could alleviate body weight and insulin resistance in obese mice. However, whether the improvement of insulin sensitivity is due to the direct modulatory effects of gut microbiota or it is the secondary effects of body weight loss still remains unknown. Adiponectin, one of the most abundant adipokines secreted from adipocytes, possesses versatile functions against a cluster of metabolic disorders including insulin resistance, fatty liver and cardiovascular diseases. What’s more, adiponectin knock out (ADN KO) mice develop severe insulin resistance compared to their wild type (WT) littermates after high fat diet (HFD) treatment. Interestingly, body weight is comparable between WT mice and ADN KO mice after HFD treatment. In this study, we used ADN KO mice to investigate the modulatory effects of gut microbiota on insulin sensitivity. Both ADN KO mice and their WT littermates were fed on either normal chow diet (NCD) and HFD for 12 weeks. Consistent with previous finding, long-term HFD treatment led to a severe insulin resistance in ADN KO mice compared to their WT littermates. In order to further explore the modulatory effect of gut microbiota on insulin sensitivity, fecal microbiota transplantation was performed. Recipient receiving microbes from ADN KO mice fed on HFD develop severe insulin resistance compared to recipient receiving microbes from WT littermates fed on HFD. Collectively, our results reveal that gut microbiota from ADN KO mice fed on HFD is sufficient to modulate insulin sensitivity in recipients, suggesting the direct regulatory effects of gut microbiota on insulin sensitivity.