Oleic acid ameliorates palmitic acid-induced ER stress and inflammation markers in naive and cerulein-treated exocrine pancreas cells.

Dietary fat overload (typical to obesity) increases the risk of pancreatic pathologies through mechanisms yet to be defined. We previously showed that saturated dietary fat induces pancreatic acinar lipotoxicity and cellular stress. The endoplasmic reticulum (ER) of exocrine pancreas cells is highly developed and thus predisposed to stress. We studied the combination of saturated and unsaturated FAs in metabolic and pancreatitis like cerulein-induced stress states on cellular ER stress.  Exocrine pancreas AR42J and rat primary exocrine acinar cells underwent acute (24hr) challenge with different FAs (saturated, monounsaturated) at different concentrations (250µM and 500µM) and in combination with acute cerulein-induced stress, and were analyzed for fat accumulation, ER stress unfolded protein response (UPR) and immune and enzyme markers. Acute exposure of AR42J and pancreatic acinar cells to different FAs and their combinations increased triglyceride accumulation. Palmitic acid significantly dose-dependently enhanced the UPR, immune factors and pancreatic lipase levels, as demonstrated by XBP1 splicing and elevation in UPR transcripts and protein levels ( Xbp1,Atf6, Atf4, Chop, Tnf a , Tgf b , Il-6 ). Exposure to high palmitic levels in a cerulein-induced stress state synergistically increased ER stress and inflammation marker levels. Exposure to oleic acid did not induce ER stress and pancreatic lipase levels and significantly decreased immune factors in an acute cerulein-induced stress state. Combination of oleic and palmitic acids significantly reduced the palmitic-induced ER stress, but did not affect the immune factor response. We show that combination of monounsaturated and saturated FAs protects from exocrine pancreatic cellular ER stress in both metabolic and cerulein-induced stress.