Associations of Circulating Irisin with FNDC5 Expression in Fat and Muscle in Type 1 and Type 2 Diabetic Mice

Irisin is an exercise-induced myokine, suggested to exert beneficial effects on metabolism. However, the studies on the regulation of irisin secretion and the expression of its precursor FNDC5 have shown conflicting data. The discrepancies among previous correlation studies in humans are related to the heterogeneity of the study population. The fact that irisin is not only a myokine but also an adipokine leads to the further complexity of the role of irisin in metabolic regulation. In this study, we examined the regulation of FNDC5 expression and irisin in circulation in both type 1 and type 2 diabetic mice, and their potential relationships with metabolic parameters. In streptozotocin (STZ)-induced type 1 diabetic mice, high-fat diet (HFD)-induced obese mice and db/db mice, the circulating irisin as well as FNDC5 gene expression in subcutaneous fat was downregulated. Muscle FNDC5 expression was only significantly lower in STZ mice, and epididymal fat FNDC5 expression was unaltered. It is interesting to note that plasma irisin levels correlated positively with subcutaneous fat FNDC5 expression, but not epididymal fat or muscle. Moreover, both irisin levels and subcutaneous fat FNDC5 correlated negatively with markers of insulin resistance. These results suggest a regulatory role for subcutaneous fat-derived FNDC5/irisin in metabolic disease.