Irisin, a secreted myokine actively cleaved from fibronectin type III domain-containing protein 5 (FNDC5), plays a crucial role in whole-body metabolism. To date, irisin receptor has not been identified, and its signal transduction is mostly unknown. Irisin is regulated by peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1-alpha (PGC1α). We previously showed that PPARγ directly regulates pancreatic lipase (PL), the principal dietary lipolytic enzyme that plays an essential role in dietary fat digestion, linking dietary fat to PL regulation. Pancreatic lipase-related protein 2 (PLRP2) sharing high homology with PL is also produced and secreted by the pancreas, although in different expression patterns and with different substrate specificity. Irisin and PL share specific nutrient regulation (fatty acids) and partial signal transduction pathway, yet the role of irisin in exocrine pancreas function is unknown. We aim to study FNDC5/irisin role in the exocrine pancreas functionality.