Decreased irisin secretion contributes to muscle insulin resistance in high-fat diet mice

Aims: Recent studies have revealed the relationship between irisin and insulin signaling, while positive associations of muscle FNDC5 with insulin resistance is observed. However, the functional mechanism of irisin on muscle insulin resistance is still obscure. This study aims to investigate the effect of irisin on muscle insulin action. Methods: Diabetic mouse model was established by high fat diet (HFD) induced obesity in C57BL/6 mice. Body indexes and serum levels of triglyceride (TG), blood glucose and insulin were record. Oral glucose tolerance test (OGTT) was performed before being killed. Circulating irisin level was also detected, while FNDC5/irisin expression was determined by RT-PCR and western blot analysis in both muscle and adipose tissues. Insulin action was further evaluated by the phosphorylation of AKT and Erk, and palmitic acid treated muscle cells were introduced for mimicking diabetic status in vitro. Results: Obvious obese feathers associated with type 2 diabetes were observed in HFD feeding mice, with decreased circulating irisin level and FNDC5/irisin secretion in adipose tissues. Although FNDC5/irisin expression showed little change in skeletal muscle, the insulin action was inhibited significantly. Moreover, palmitic acid treated muscle cells showed similar inhibition of insulin action, and FNDC5/irisin expression change. Besides, insulin action could be reversed by irisin addition in muscle cells. Conclusion: HFD induced obese mice showed decreased irisin secretion from adipose tissues, which might contribute to muscle insulin resistance. Furthermore, irisin addition could recover insulin action in palmitic acid treated muscle cells, indicating the importance of irisin for preserving insulin signaling.