Fat-induced changes of the integrity of rat exocrine pancreas measured in vivo and in vitro

Abstract

Adaptation of exocrine pancreas by dietary fats and its resulting effects on morphology and function of the exocrine pancreas remain controversial. In this study we have examined the influence of dietary fats on pancreatic pathophysiology by examining the basal and stimulated pancreatic secretion of enzymes in response to high fat (HFD) and no fat (NFD) diets. Methods: Male Sprague Dawley rats (N=10) were fed ad libitum with high fat diets containing 45% fat (vegetable oil) and 29% carbohydrates. An identical group was fed with diets containing 58% carbohydrates but no fat. The animals were maintained in screen bottomed cages at 22°C on a 12 hr light-dark cycle with free access to water. After four weeks, the animals were fasted for 24 hrs, anesthetized, bile pancreatic duct was cannulated to collect pancreatic juice. Bile pancreatic juice was collected for 30 min before and after infusion of CCK for 30 min via the jugular vein. The animals were maintained for additional 24 hrs with recirculation of pancreatic juice to the duodenum and then sacrificed to isolate pancreatic acini by collagenase digestion. Amylase content and release in response to CCK-8 by isolated acini were measured. Histopathologic studies of pancreas, fixed in 10% buffered formalin, were evaluated by light microscopy. Results: Outputs of enzymes (amylase, lipase and trypsinogen) in bile pancreatic juice of rats on high fat diets under basal and stimulated conditions were significantly higher than that of rats on no fat diet. Amylase release measured in isolated acini of rats on high fat diet in response to CCK-8 was significantly lower than that of rats on no-fat diet. Histopathology revealed significant difference in cellular changes (cytoplasmic vacuolation; swelling and pyknosis) in rats on high fat diet. Conclusions: Dietary fats, especially high fat, alters pancreatic morphology and function. The results indicate that high fat diets enhanced the outputs of enzymes in bile pancreatic juice, down regulated CCK stimulated amylase response in isolated pancreatic acini and induced cellular injury.