Exercise-induced FNDC5/Irisin Activation Drives Brown-like Adipocyte Phenotype in Visceral Adipose Tissue from Obese Rats

Abstract

Exercise-stimulated myokines have pleiotropic effects in several tissues, including white adipose tissue (WAT). The recently discovered FNDC5/irisin is secreted into circulation in response to exercise and might induce brown adipocytes-in-WAT, which has been associated with greater whole-body energy expenditure. However, the role of exercise on FNDC5/irisin levels remains unclear. PURPOSE: To investigate whether voluntary physical activity (VPA) and endurance training (ET) induce brown-adipocyte phenotype in visceral WAT from obese rats. METHODS: Sprague-Dawley rats were allocated into sedentary, VPA and ET groups fed with a standard (STD, 35%Kcal-derived fat) or high-fat diet (HFD, 71% Kcal-derived fat) during 17 wks. VPA-animals had free access to running wheel during the study. After 9 wks of hypercaloric-diet feeding, ET-animals were submitted to 8-wks treadmill while maintained dietary treatments. Gastrocnemius muscle was removed for FNDC5 protein determination by Western Blot. Visceral WAT depots were weighted and epididymal (eWAT) was used to determine mRNA levels of Bmp7, Tmem26 and Cidea by qPCR. Diet and exercise effects were performed using two-way ANOVA. RESULTS: The caloric intake and body weight did not differ significantly between diet groups (p>0.05). HFD-induced increase in visceral adiposity (9±0.2 vs. 10.8±0.4%, p0.05). VPA had no impact either on gastrocnemius FNDC5 protein or on eWAT Bmp7, Tmem26 and Cidea gene expression (p>0.05). Although no alterations in Bmp7 and Tmem26, ET induced an increase of Cidea expression in obese animals (43.2±17.7 vs. 216.9±20.1%, p<0.01), which was positively associated with gastrocnemius FNDC5 (p<0.001; r=0.7) and negatively associated with visceral adiposity (p<0.001; r=-0.79). CONCLUSIONS: Taken together, ET-related increase in skeletal muscle FNDC5 protein could, at least, mediates brown-like adipocyte phenotype in eWAT from obese rats, which was also associated with reduced visceral fat accumulation.