The time-course response of rat pancreatic enzymes to a diet containing 25% sunflower oil was investigated. A 1.2-fold enhancement in lipase specific activity was observed as early as the first day of diet consumption and was further increased up to 1.9-fold on the 5th day. On the other hand, colipase activity was slightly decreased during the first two days of high-lipid diet intake and then increased. An immediate and direct effect was also exerted by the 25% lipid diet on lipase biosynthesis. Both fractional synthetic rate and specific activity of lipase were comparably induced. Due to a 1.6-Sold increase in the overall protein synthesis following 5 days of lipid diet comsumption, the absolute synthesis of lipase and amylase was increased by 3.5-fold and 0.98-fold, respectively, as compared to control animals. By contrast, the synthesis of procarboxypeptidases and serine proteases did not increase before day 5, probably as the result of a distinct adaptative mechanism. The pancreactic mRNA levels in control and adapted animals, which were determined by dot-blot hybridization with amylase and lipase cDNAs, were consistent with a biphasic induction of lipase synthesis since a first increase in the level of the enzyme-specific mRNA during the first two days of diet intake (4-fold on day 1) was followed by a second increase after the fourth day (6.5-fold on day 5). On the other hand, amylase mRNA level was unchanged during the dietary manipulation. Thus, hyperlipidic diets exerted an immediate effect on both lipase activity and synthesis but a delayed effect on procarboxypeptidase and serine protease synthesis. In a similar manner, the immediate induction of lipase mRNA level by dietary fat, followed by another increase a few days later, suggested that at least two different mechanisms are involved in lipase mRNA induction.The concentration of pancreatic lipase is readily increased by fat-rich diets, the adjustment magnitude being governed by factors such as the amount [l -41 and type [4, 51 of lipids, as well as the total percentage of calories as fat in the diet [6]. Although the causal mechanisms still remain elusive, recent animal experiments suggested that secretion might play a major part in this adaptation since ingestion of fat resulted in the release of secretin [7 -91. Furthermore, the adaptative response patterns of pancreatic enzymes to dietary fat [I] and secretin [lo, 111 were found to be similar.Pancreatic lipase adaptation is a rapid process since a fourfold increase in the enzyme specific activity could be measured in the pancreas of just-weaned rats after the ingestion of a lard-rich diet for two days only [12]. The most significant adjustment in lipase specific activity, a six-fold increase as compared with control rat, occurred after the fourth day. It was therefore interesting to try to define better the early response of pancreatic enzymes to dietary Sat in adult rats in terms of activity and levels of the corresponding mRNAs. The purpose of the present report was to study the time-course r...