Endocrine Abstracts

The myokine irisin is secreted after cleavage of the transmembrane protein Fibronectin type III domain-containing protein five and was shown to induce a thermogenic program in white adipose tissue. This cleavage can be induced by exercise, thus linking exercise with browning of adipose tissue. We investigated the response of Fndc5/irisin as well as its inducer Peroxisome proliferator-activated receptor gamma co-activator 1α (Ppargc1a) in mice long-term selected for high treadmill performance. Male mice were randomly assigned to either a sedentary control group (CO), a group with free access to a running wheel (RW), or a treadmill exercise group (TM). mRNA and protein abundances of Fndc5 and Ppargc1a in muscle tissue as well as presence of irisin in blood and muscle were investigated. Western blot analyses were performed using antibodies being able to differentiate between irisin at ~12 kDa and full-length Fndc5 at ~25 kDa. Irisin abundance was significantly higher in muscle and serum of TM group mice immediately after exercise. Compared to the CO group, mRNA expression of transcripts 3 and 4 of Ppargc1a was up-regulated in the TM group (33- and 9-fold respectively). However, Fndc5 mRNA remained unchanged immediately after exercise. Furthermore, neither Fndc5 nor Ppargc1a protein was elevated in muscle tissue. The Ppargc1a-Fndc5/irisin pathway did not clearly respond to mild exercise in the RW group. Our results indicate that irisin cleavage and secretion increases rapidly after acute but not after moderate voluntary exercise in our mouse model. The relatively high basal level of irisin in skeletal muscle and serum indicates a constant, physiological Ppargc1a-independent irisin production and secretion. Ppargc1a induction as well as irisin production and secretion in response to acute exercise may be involved in the metabolic adaptation to high endurance capacity.