Metformin in combination with genistein ameliorates skeletal muscle inflammation in high-fat diet fed c57BL/6 mice

Abstract

Although the beneficial effects of metformin (MET) and genistein in ameliorating inflammation have been elucidated, their combined impacts on skeletal muscle inflammation have not been clearly understood. This study aimed to examine the possible preventive effect of MET in combination with genistein on skeletal muscle inflammation in high-fat diet (HFD) fed C57BL/6 mice. Fifty C57BL/6 male mice were fed on an HFD for 10 weeks. The mice were categorized into five groups, control, HFD, HFD + MET (0.23%), HFD + genistein (0.2%), and HFD + MET + genistein for 12 weeks. The results showed that treatment with MET and genistein, either alone or in combination, led to reduced weight gain, fasting blood glucose, plasma insulin, HOMA-IR levels, and Area Under the Curves (AUCs) in ipGTT. MET in combination with genistein demonstrated a decreasing effect on macrophages infiltration rate compared to genistein and MET groups alone. The expression of iNOS was reduced, whereas the expression of M2 macrophage markers was increased in combined treatment of MET and genistein. Furthermore, MET in combination with genistein reduced the expression of TNF-α, IL-1β, MCP-1, and IL-6 and increased the expression of IL-10 in comparison with genistein and MET groups alone. Plasma and skeletal muscle triglycerides and intra-myocellular lipid deposition were reversed by treatment with MET and genistein, alone or in combination. These results imply that the combination therapy of MET and genistein may have therapeutic potential for decreasing obesity-induced skeletal muscle inflammation in the HFD-fed model.

Keywords: Cytokines; Genistein; Macrophages; Metformin; Skeletal muscle inflammation.