Elevated skeletal muscle irisin precursor FNDC5 mRNA in obese OLETF rats

Objective. There is debate as to whether fibronectin type III domain containing 5 (FNDC5)and its protein product irisin are therapeutic targets for obesity-associated maladies. Thus,we sought to examine FNDC5 mRNA within skeletal muscle of obese/diabetic-prone OtsukaLong-Evans Tokushima Fatty (OLETF) rats versus lean/healthy Long Evans TokushimaOtsuka (LETO) rats. We hypothesized that FNDC5 expression would be greater in obese(OLETF) versus lean (LETO) animals.Materials/Methods. Triceps muscle of 30–32 week old OLETF and LETO rats were assayedfor FNDC5 and PGC1α mRNA levels. Body composition and circulating biomarkers of theOLETF and LETO rats were also correlated with skeletal muscle FNDC5 mRNA expressionpatterns in order to examine potential relationships that may exist.Results. OLETF rats exhibited twice the amount of triceps FNDC5 mRNA compared toLETO rats (p<0.01). Significant positive correlations existed between triceps muscle FNDC5mRNA expression patterns versus fat mass (r=0.70, p=0.008), as well as plasma leptin (r=0.82, p<0.001). PGC1α mRNA levels were also highly correlated with FNDC5 mRNA (r=0.85,p<0.001). In subsequent culture experiments, low and high physiological doses of leptin hadno effect on PGC1α mRNA or FNDC5 mRNA levels in C2C12 myotubes. Paradoxically,circulating irisin concentrations tended to be higher in a second cohort of LETO versusOLETF rats (p=0.085).