Antiviral therapy 2016 Oct 11() doi 10.3851/IMP3099
Any strategy designed to decrease the macrophage content in adipose tissue (AT) is of great value as a way to decrease inflammation in this fat depot and also as a way to prevent or treat obesity and associated disorders. Maraviroc (MVC), a CCR5 antagonist approved for the treatment of HIV-infected patients, has beneficial effects on metabolism. The objective of this study was to investigate the effects of MVC on AT macrophage recruitment in a mouse model of obesity. The plausible underlying mechanisms of action were also investigated.
32 male C57BL/6 mice were randomly assigned to the following groups: i) Control, ii) MVC (300 mg/L MVC in drinking water) iii) High fat diet (HFD) or iv) HFD+MVC. After 16 weeks of treatment, histopathological and molecular analyses were performed on epidydimal fat.
Our results demonstrated that MVC reduced the presence of macrophages in epididymal fat despite the ingestion of a HFD. The inhibition of MCP-1 gene expression and JNK signaling pathway along with the upregulation of protective cytokines such as cardiotrophin-1 could contribute to these actions. MVC effects on AT macrophage recruitment were associated with a lower body weight gain and a partial improvement in insulin resistance despite a HFD.
We have demonstrated the ability of MVC to ameliorate the increased AT macrophage recruitment induced by a HFD in a mouse model of obesity. These actions could be of interest when designing antiretroviral treatments in HIV-patients.