M2 macrophages infusion ameliorates obesity and insulin resistance by remodeling inflammatory/macrophages' homeostasis in obese mice

- M2 macrophage, anti-inflammatory, infusion ameliorated both obesity and obesity-related insulin resistance.
- Infused M2 was homed to epididymal adipose tissue (EAT) to reverse the inflammatory/macrophages' homeostasis.
- Reverse inflammatory/macrophages' homeostasis contributed to decreased activation of MCP1-CCR2+CX3CR1lowLy6C+ system.
- Increased M2 in EAT promoted the expression of the thermogenic mechanism to relieve insulin resistance.

ObjectiveThe role of M2 macrophages infusion in dealing with obesity is still little known. In this study, the therapeutic effects of M2 macrophages infusion were investigated.MethodsHigh fat diet (HFD) was used to induce obesity in C57BL/6N mice. 5 × 105 M2 macrophages, derived from the bone marrow, were injected into obese mice through the tail vein twice with an interval of one week.ResultsOne week after the second injection, weight of inguinal adipose pad was significantly decreased. Accordingly, the adipocyte size of epididymal and inguinal adipose tissue (EAT and INAT) shrank. To our interest, we found that the infused M2 macrophages were homed to EAT, reversing the disturbed homeostasis of high M1 to low M2 in obese mice. Meanwhile, EAT with remodeled macrophages' homeostasis expressed less MCP-1, accompanying with decreased recruitment of inflammatory CCR2+CX3CR1lowLy6C+ monocytes from the blood in M2 infusion group. Further, increased M2 in EAT contribute to enhanced expression of UCP1 expression in EAT, which helped to ameliorate insulin resistance and, subsequently, improve the serum level of triglycerides (TG) and low density lipoprotein cholesterol (LDL-c).ConclusionsThese findings highlighted that M2 macrophages infusion could ameliorate obesity as well as obesity-related insulin resistance, suggesting an effective and healthy weight loss strategy.