Pancreatitis is an FGF21-deficient state that is corrected by replacement therapy
Genaro Hernandez, Ting Luo, Tanveer A. Javed, Li Wen, Michael A. Kalwat, Kevin Vale, Farah Ammouri, Sohail Z. Husain, Steven A. Kliewer, David J. Mangelsdorf
Abstract
promoter. Consistent with the mouse studies, we also observed the reciprocal expression of ATF3 and FGF21 in the pancreata of human patients with pancreatitis. Using three different mouse models of pancreatitis, we showed that pharmacologic replacement of FGF21 mitigated the ISR and resolved pancreatitis. Likewise, inhibition of the ISR with an inhibitor of the PKR-like endoplasmic reticulum kinase (PERK) also restored FGF21 expression and alleviated pancreatitis. These findings highlight the importance of FGF21 in preserving exocrine pancreas function and suggest its therapeutic use for prevention and treatment of pancreatitis.