Abstract
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.
Highlights
We have examined the relevance of circulating irisin and tissue fibronectin typeIII domain-containing protein 5 (FNDC5) expression to glucose and lipid metabolism
The question of which tissue contributes more to circulating irisin and metabolic regulation in diabetes has been delineated through correlation analysis
We and others have confirmed that in healthy human individuals, muscle mass is an independent predictor of circulating irisin [12,13], which may be important in light of the well-characterized phenomenon of age-related muscle atrophy [39]
Summary
Irisin is known to be dependent on proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), a major mediator of the effect of exercise in muscle [2]. In the original report by Bostrom et al, PGC1α overexpression led to the increased expression of FNDC5, which is secreted as irisin into circulation by exercise [1]. The discovery of irisin has highlighted the vital role of crosstalk between muscle and other tissues, such as adipose tissue, liver, and bone, in the regulation of metabolism [3]. It has been proposed that irisin mediates the beneficial effects of exercise on metabolism by upregulation of uncoupling protein 1 (UCP1) expression and the subsequent elevation of energy expenditure, resulting in the amelioration of obesity-induced insulin resistance [4,5]
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