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Enterostatin, a gut-brain pentapeptide cleaved from procolipase has been shown to inhibit fat intake in rodents after both peripheral and central administration. In this study, the effect of intracerebroventricular (ICV) injection of enterostatin on fat intake was investigated in neonatal chicks. In Experiment 1, 3-h-fasted chicks fed a low-fat diet were injected with the various doses of enterostatin. Experiment 2 was similar to experiment 1 except that the birds were fasted overnight. In Experiment 3, the 3-h-fasted and in Experiment 4, the overnight fasted chicks adapted to a high-fat diet received different doses of enterostatin. ICV injection of enterostatin caused a dose-dependent increase in high-fat diet intake in 3-h-fasted chicks whereas a decrease in high-fat intake was observed in chicks that were fasted overnight. However, low-fat diet intake was not affected by enterostatin in either 3-h or overnight fasted chicks. These results suggest that enterostatin acts within the brain of chicks to influence fat intake. It appears that in chicks, the eating effect of enterostatin has a biphasic nature similar to those seen in rodents., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The most widely used pharmacological therapies for obesity and weight management are based on inhibition of gastrointestinal lipases, resulting in a reduced energy yield of ingested foods by reducing dietary lipid absorption. Colipase-dependent pancreatic lipase is believed to be the major gastrointestinal enzyme involved in catalysis of lipid ester bonds. There is scant literature on the action of pancreatic lipase under the range of physiological conditions that occur within the human small intestine, and the literature that does exist is often contradictory. Due to the importance of pancreatic lipase activity to nutrition and weight management, the present review aims to assess the current body of knowledge with regards to the physiology behind the action of this unique gastrointestinal enzyme system. Existing data would suggest that pancreatic lipase activity is affected by intestinal pH, the presence of colipase and bile salts, but not by the physiological range of Ca ion concentration (as is commonly assumed). The control of secretion of pancreatic lipase and its associated factors appears to be driven by gastrointestinal luminal content, particularly the presence of acid or digested proteins and fats in the duodenal lumen. Secretion of colipase, bile acids and pancreatic lipase is driven by cholecystokinin and secretin release.

Enterostatin (APGPR) is a pentapeptide released from its precursor protein, procolipase. We found for the first time that enterostatin has memory-enhancing activity. Enterostatin enhanced memory consolidation after central or oral administration at a dose of 10 nmol/mouse or 300 mg/kg, respectively, in a step-through type passive avoidance test in mice. The memory-enhancing activity of enterostatin was inhibited by pretreatment with lorglumide, an antagonist for cholecystokinin 1 (CCK1) receptor. However, enterostatin had no affinity for CCK receptors. These results suggest that enterostatin improves memory retention through CCK release.

A primary function of the pancreas is to produce digestive enzymes that are delivered to the small intestine for the hydrolysis of complex nutrients. Much of our understanding of digestive enzymes comes from studies in animals. New technologies and the availability of the sequence of the human genome allow for a critical review of older reports and assumptions based on animal studies. This report updates our understanding of human pancreatic digestive enzymes with a focus on new insights into the biology of human proteases, lipases and amylases.

Serotonin (5-HT) is considered to play an important role in control of appetite. Enterostatin has been shown to alter 5-HT release in the brain, and non-specific 5-HT antagonists blocked the anorectic response to icv enterostatin. The aim of this study was to further identify which 5-HT receptor subtype mediates the enterostatin feeding behavior and whether this effect occurs due to action in the PVN. Wild-type and 5-HT2C receptor-/- (KO) mice and normal Sprague-Dawley rats were used in these experiments. All animals were fed a high fat diet. Enterostatin (120 nmol, i.p.) reduced the intake of high fat diet in 5-HT2C receptor mutant mice (saline 4.54 +/- 0.47 kcal vs. Ent 2.53 +/- 0.76 kcal) 1 h after injection. A selective 5-HT1B antagonist (GR55526, 40 mg/kg body weight, i.p.) blocked the enterostatin hypophagic effects in these KO mice. Rats were implanted with cannulas into the amygdala and the ipsilateral PVN. The 5-HT receptor antagonists metergoline (non-specific receptor subtypes 1 and 2), or ritanserin (selective 2C), or GR55562 (selective l B) was injected into the PVN prior to enterostatin (0.01 nmol) injection into the amygdala. Enterostatin reduced food intake (saline: 5.80 +/- 0.59 g vs. enterostatin 3.47 +/- 0.56 g, P < 0.05 at l h). Pretreatment with either metergoline (10 nmol) or GR55526 (10 nmol) but not ritanserin (10 nmol) into the PVN attenuated the anorectic response to amygdala enterostatin. The data imply that the enterostatin anorectic response may be modulated by 5-HT1B receptors and that a neuronal pathway from the amygdala to the PVN regulates the enterostatin response through activation of 5-HTlB receptors in PVN.

A high-fat diet easily promotes hyperphagia giving an impression of an uncontrolled process. Fat digestion itself however provides control of fat intake through the digestion itself, carried out by pancreatic lipase and its protein cofactor colipase, and through enterostatin, a peptide released from procolipase during fat digestion. Procolipase (-/-) knockout mice have a severely reduced fat digestion and fat uptake, pointing to a major role of the digestive process itself. With a normal fat digestion, enterostatin basically restricts fat intake by preventing the overconsumption of fat. The mechanism for enterostatin might be an inhibition of a mu-opioid-mediated pathway, demonstrated through binding studies on SK-N-MC-cells and crude brain membranes. Another target protein of enterostatin is the beta-subunit of F1F0-ATPase, displaying a distinct binding of enterostatin, established through an aqueous two-phase partition system. The binding of enterostatin to F1-ATPase was partially displaced by beta-casomorphin, a peptide stimulating fat intake and acting competitively to enterostatin. We frame a hypothesis that regulation of fat intake through enterostatin contains a reward component, which is an F1-ATPase-mediated pathway, possibly complemented with an opioidergic pathway.

In vitro, pancreatic triglyceride lipase requires colipase to restore activity in the presence of inhibitors, like bile acids. Presumably, colipase performs the same function in vivo, but little data supports that notion. Other studies suggest that colipase or its proform, procolipase, may have additional functions in appetite regulation or in fat digestion during the newborn period when pancreatic triglyceride lipase is not expressed. To identify the physiological role of procolipase, we created a mouse model of procolipase deficiency. The Clps-/- mice appeared normal at birth, but unexpectedly 60% died within the first 2 weeks of life. The survivors had fat malabsorption as newborns and as adults, but only when fed a high fat diet. On a low fat diet, the Clps-/- mice did not have steatorrhea. The Clps-/- pups had impaired weight gain and weighed 30% less than Clps+/+ or Clps+/- littermates. After weaning, the Clps-/- mice had normal rate of weight gain, but they maintained a reduced body weight compared with normal littermates even on a low fat diet. Despite the reduced body weight, the Clps-/- mice had a normal body temperature. To maintain their weight gain in the presence of steatorrhea, the Clps-/- mice had hyperphagia on a high fat diet. Clps-/- mice had normal intake on a low fat diet. We conclude that, in addition to its critical role in fat digestion, procolipase has essential functions in postnatal development and in regulating body weight set point.

Enterostatin may be involved in the preference for fat and the control of fat intake. Using two different feeding patterns, we observed a change in food intake after injection of enterostatin (VPDPR) into the third ventricle. When rats were adapted to free selection choice between low fat (LF) and high fat (HF) diets, VPDPR inhibited intake of the LF diet at 100, 200 and 800 ng and inhibited intake of the HF diet at 200 ng. The dose-response of HF diet intake to VPDPR was U-shaped. However, even the optimal dose (200 ng), which reduced the intake of both LF and HF diets when both diets were given together, was not effective when the LF diet was given alone. In the present study, VPDPR has also shown to not affect plasma glucose or insulin levels. These results suggest that exogenous VPDPR may inhibit appetite when endogenous enterostatin secretion is increased by ingestion of dietary fat, and that VPDPR has a limited range of effects on feeding behavior. We support the hypothesis that the early satiety sense of VPDPR as an anorectic agent in a central site is directly related to endogenous enterostatin or procolipase levels after fat intake, but not glucose or insulin levels.

Procolipase is secreted as a protein consisting of 101 amino acids. In the intestinal lumen, procolipase is activated by trypsin and cleaves to form the active colipase and the pentapeptide from the amino terminus. This pentapeptide is called enterostatin. Pancreatic procolipase synthesis is stimulated by a high-fat diet. A large body of evidence has been gathered in the past decade demonstrating the role of enterostatin in the inhibition of food intake; in particular, fat intake. This aspect of enterostatin will be discussed in this review. Other functions of enterostatin such as the inhibition of insulin secretion, will not. Apolipoprotein AIV is a protein synthesized by the human intestine. Similar to procolipase, the synthesis and secretion of apo AIV are also stimulated by fat absorption. In 1992, Fujimoto et al. first demonstrated that apo AIV is a satiety signal secreted by the small intestine following the ingestion of a lipid meal. Subsequently, this initial observation was followed by a number of studies supporting apo AIV's role in the inhibition of food intake. This review will discuss the role of apo AIV in inhibiting food intake., (Copyright 1999 Harcourt Publishers Ltd.)

A high fat intake, together with an inability to match lipid oxidation to fat intake, has been found to be correlated with obesity in humans. This review describes our current understanding of enterostatin, a peptide that selectively reduces fat intake. Enterostatin is formed in the intestine by the cleavage of secreted pancreatic procolipase, the remaining colipase serving as an obligatory cofactor for pancreatic lipase during fat digestion. Enterostatin is also produced in the gastric mucosa and the mucosal epithelia of the small intestine. Procolipase gene transcription and enterostatin release into the gastrointestinal lumen are increased by high-fat diets. After feeding, enterostatin appears in the lymph and circulation. Enterostatin will selectively inhibit fat intake during normal feeding and in experimental paradigms that involve dietary choice. Its anorectic effect has been demonstrated in a number of species. Both peripheral and central sites of action have been proposed. The peripheral mechanism involves an afferent vagal signaling pathway to hypothalamic centers. The central responses are mediated through a pathway that includes both serotonergic and opioidergic components. Chronically, enterostatin reduces fat intake, bodyweight, and body fat. This response may involve multiple metabolic effects of enterostatin, which include a reduction of insulin secretion, an increase in sympathetic drive to brown adipose tissue, and the stimulation of adrenal corticosteroid secretion. A possible pathophysiological role is suggested by studies that have linked low enterostatin production and/or responsiveness to strains of rat that become obese and prefer dietary fat. Humans with obesity also exhibit a lower secretion of pancreatic procolipase after a test meal, compared with persons of normal weight.

Dietary fats affect health and disease. The assimilation of dietary fats into the body requires that they be digested by lipases. One lipase, pancreatic triglyceride lipase, is essential for the efficient digestion of dietary fats. Pancreatic triglyceride lipase is the archetype of the lipase gene family that includes two homologues of pancreatic triglyceride lipase, pancreatic lipase-related proteins 1 and 2. In recent years, important advances have been made in delineating the mechanisms of lipolysis. The cDNA sequences encoding pancreatic triglyceride lipase and the related proteins have been described. The tertiary structure of human pancreatic triglyceride lipase has been determined alone and in a complex with colipase, a pancreatic protein required for lipase activity in the duodenum. This structural information has allowed the rational design of site-specific mutants of pancreatic triglyceride lipase. Together with the structural information, these mutants have greatly advanced our understanding of the molecular details governing lipolysis. This review describes these studies, which will eventually provide the background for the rational design of nutrition therapy in patients with pancreatic insufficiency and fat malabsorption.

Enterostatin has previously been reported to alter serum insulin and corticosterone levels after central administration of the peptide. The purpose of the present study was to investigate the effect of peripheral administration of enterostatin on insulin and corticosterone levels as well as the response of plasma insulin to enterostatin administration in adrenalectomized rats. Female Sprague-Dawley rats were given a bolus injection intravenously with enterostatin alone or together with glucose. Enterostatin increased basal plasma levels of insulin, but significantly inhibited the increase in plasma insulin stimulated by glucose. Plasma corticosterone levels were not altered after a single intravenous injection of enterostatin. In rats infused chronically with enterostatin, plasma insulin levels were significantly reduced and plasma corticosterone levels were increased. The daily food intake was lower in these rats, but there was no effect on body weight. After adrenalectomy, the responsiveness of plasma insulin to enterostatin infusion was completely abolished. Furthermore, adrenalectomy itself reduced basal plasma levels of insulin and increased plasma levels of endogenous enterostatin. These results suggest that peripheral enterostatin administration produces a similar effect as central infusion of the peptide, and that the glucocorticoid hormones are involved in the regulation of plasma insulin by enterostatin.

Background: Ethanol ingestion may disturb fat digestion and absorption by affecting gastric, intestinal, hepatic, and pancreatic functions. Involved mechanisms are not well understood. We examined in vitro ethanol effects on gastric and pancreatic lipolytic activity., Methods: Human gastric juice, pure gastric lipase, pancreatic lipase, colipase, carboxyl ester lipase, phospholipase A2, and duodenal contents were a) preincubated at 37 degrees C with ethanol (0-30%) and then assayed under normal conditions (pH-stat titration), or b) assayed in the presence of various ethanol concentrations (0-30%)., Results: Ethanol reduced gastric and pancreatic lipolytic activities in a dose-dependent manner. The effect was more pronounced with alcohol present in the assay medium, with 5% ethanol reducing carboxyl ester lipase activity by 10%, gastric lipase activity by 20%, and pancreatic lipase activity by 46%. Colipase and phospholipase A2 activities were only slightly affected by ethanol., Conclusions: Observed effects of ethanol on gastric and pancreatic lipase may be important when fat digestion is already impaired due to gastric, intestinal hepatic, and/or pancreatic diseases.

The time course of feeding, grooming, exploration, and sleeping behaviors has been measured following treatment with enterostatin, the signal pentapeptide from procolipase. The peptide was injected intraperitoneally prior to presenting food, and the frequency of feeding and grooming activity, drinking, and rest or sleeping were observed at 10-s intervals for 60 min. Enterostatin did not delay the onset of feeding but shortened the time spent eating compared to saline injected controls. Conversely, grooming activity appeared earlier following enterostatin, activity was reduced, and resting behavior occurred earlier with this peptide. There were no changes in the drinking behavior. For the first hour following enterostatin, eating represented 20.8% of the time, grooming 9.2%, activity 18.3%, and rest or sleep 47.2%, with drinking making up the other 4.4%. In contrast, saline-injected animals ate for 27.1% of the time, groomed for 12.4%, were active 28.5% of the time, had sleep or rest time equal to 27.9%, and drank for 4.1% of the time. In fasted animals, the onset of grooming, the decrease in activity, and the increase in time sleeping occurred earlier than with saline. These studies support the concept that enterostatin decreases food intake by producing early satiety.

A significant increase in synthesis of pancreatic colipase in streptozotocin (STZ)-induced diabetes in rats has been demonstrated previously. The aim of the present study was to identify whether this change in colipase synthesis was related to a pretranslational or translational regulation. The levels of colipase, lipase, and amylase mRNA were determined by Northern blot hybridization. The enzymatic activities and synthesis rates for these proteins were determined. One week after injection of STZ, the mRNA levels for both colipase and lipase were increased by about 100% over control, with accompanying increases in enzyme synthesis rates and enzymatic activities. The amylase mRNA, amylase synthesis rates, and amylase activity decreased by 95%. Insulin injection at a dose of 2 U/100 g/day for 5 days restored enzyme mRNA levels as well as enzyme activities. Kinetic studies revealed that lipase mRNA rapidly increased after induction of diabetes, closely followed by increases in lipase synthesis rates and lipase content. Colipase mRNA also rapidly increased, with values 60, 85, and 82% over control 1, 2, and 3 days after STZ injection, respectively. But the colipase synthesis rate increased slowly, being only 10, 20, and 40% over control 1, 2, and 3 days after STZ treatment, respectively. Colipase content did not increase until 4 days after STZ injection (3 days after the increase in colipase mRNA). The decrease in amylase mRNA was paralleled by decreases in amylase synthesis rates and amylase content. In conclusion, the increase in colipase content in STZ-induced diabetes in rats is a consequence of enhanced transcriptional or pretranslational regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Valine-proline-aspartate-proline-arginine (VPDPR), the amino terminal pentapeptide of pancreatic procolipase, produced a dose-dependent reduction in food intake when injected intraperitoneally into Osborne-Mendel rats that had been starved overnight. This inhibition of feeding was observed when the rats were fed a high-fat diet but not in rats fed a high-carbohydrate, low-fat diet. At higher doses of VPDPR, the inhibition of feeding was maintained for over 6 hours. An equimolar mixture of the free amino acids had no effect on food intake. In rats adapted to a three-choice macronutrient diet, VPDPR inhibited fat intake but had no effect on carbohydrate or protein intake. This selective inhibition of fat intake was observed in both overnight-fasted rats presented with food and in ad-lib-fed rats at the beginning of the dark-onset feeding period. It is suggested that this peptide may be a feedback signal to regulate the intake of dietary fat.

Pancreatic procolipase is activated by trypsin forming colipase, a cofactor for pancreatic lipase involved in intestinal fat digestion and a pentapeptide named enterostatin. Enterostatin with the sequence Val-Pro-Asp-Pro-Arg (VPDPR) was previously shown to decrease food intake in rats both after peripheral and central injection. In this work enterostatin has been shown to reduce specifically the consumption of a high-fat diet as opposed to a low-fat diet after central injection of Sprague-Dawley rats. After starvation for 18 hours the rats were given a free choice of a low-fat diet (5.2% fat by weight; 14.1% by energy) and a high-fat diet (17.8% fat by weight; 32.8% by energy) in separate containers. After injection of 200 ng of VPDPR into the lateral ventricle, the rats selectively decreased the intake of the high-fat diet by 45% (p less than 0.005), while the intake of the low-fat diet was unaffected compared to saline injection. VPDP after intracerebroventricular injection had totally lost the selective effect on the consumption of a high- fat and a low-fat diet. It is suggested that enterostatin formed during fat digestion from pancreatic procolipase may provide a feed-back signal for the intake of lipid.

In the oral exocrine pancreatic function test using fluorescein dilaurate, this synthetic substrate attaches primarily to the triglyceride surfaces of the neutral lipids administered as part of the breakfast: these fluorescein dilaurate molecules cannot be attacked by cholesterol esterase. In the course of triglyceride saponification by lipase and colipase, however, the fluorescein dilaurate is liberated and hydrolyzed by cholesterol esterase. The pancreatic function test, therefore, measures the lipolytic activities not merely of cholesterol esterase, but indirectly of lipase, as well.

Pancreatic lipase readily adsorbs to a triglyceride droplet. In the intestine the triglyceride droplets are covered with bile salt and phospholipids which will prevent the adsorption of lipase. In this situation the activity of lipase is restored by colipase, another pancreatic protein. Lipase and colipase in solution form a 1:1 molar complex. I emphasize the fact that the binding and conformation of the two proteins in the complex is dependent on the type of lipids present and suggest that this lipid-determined structure of the complex is responsible for the actual function of lipase/colipase. It determines whether colipase assists lipase in binding to the bile salt-covered triglyceride droplet as is the case with tributyrin as substrate, and whether colipase in addition activates lipase as is the case with a mixed trioctanoin/lecithin monolayer substrate. In other words, lipase activity is regulated by the combined action of colipase and the lipid substrate.

Even though most of the major controversies regarding intestinal fat absorption have been resolved over the past three decades, our concepts of fat digestion and absorption continue to be modified, and new concepts have emerged. The purpose of this review is to summarize advances in our understanding of fat digestion and absorption since the topic was last reviewed by Johnston in 1968. The discussion will emphasize 1) the role of colipase and its interactions with lipase, bile salt micelle, and triglyceride substrate; 2) the importance of the unstirred water layer in fat absorption; 3) micellar formation and dissociation; 4) the role of fatty acid binding protein; 5) factors influencing the reesterification mechanisms in the intestine; and 6) intestinal contribution to lipoprotein and apoprotein production. The importance of these new concepts and the remaining gaps in our understanding of these complex digestive and absorptive processes are discussed.

Zonal high-performance affinity chromatography has been used in order to study the interactions between pig isolipases A, B and C and the terminal peptide chain fragment 336-449 of the pig lipase on the one hand, and the homolog colipase bound to the inert LiChrosorb diol support on the other. A mathematical treatment led the to assessment of the dissociation constant of the lipase-colipase complex using isolipases or the terminal peptide as eluted acceptors and colipase as silica-bound ligand (Mahé, N., Léger, C.L., Linard, A. and Alessandri, J.-M. (1987) J. Chromatogr. 395, 511-521). A higher affinity of isolipase B as compared to isolipases A and C towards colipase was observed (KD, respectively, of 0.68, 11 and 12 microM) at pH 6.5. Under the same chromatographic conditions, the terminal peptide chain interacted with the bound colipase (KD 0.70 microM, close to that of isolipase B). The chromatographic behaviors of both native and chemically modified lipase and terminal peptide were very similar. In particular, guanidination of lysine residues of both peptide and isolipase B led to the loss of interactions with colipase. The same result was observed with the peptide preincubated in the presence of increasing amounts of free colipase. Accordingly, it is suggested that, firstly, a preferential association of isolipase B to colipase could take place and, secondly, the colipase recognition site of lipase could be located in the C-terminal region, the conformational structure of the terminal peptide not being affected by the enzymic cleavage and, therefore, being largely independent of the rest of the polypeptide molecule. On the other hand, a lower colipase affinity for isolipases A or C than for isolipase B or the C-terminal peptide could tentatively be attributed to a non-local (distant) disturbing effect of the negatively charged glycan chain, as sialic acid is present in both isoforms A and C. Finally, the present paper confirms and extends earlier studies on lipase-colipase interactions.

Pancreatic procolipase is a cofactor for lipase and necessary for optimal fat digestion in the intestine during a meal. It is activated by trypsin in the intestine during release of an activation peptide, with the sequence Val-Pro-Asp-Pro-Arg in rat. This peptide, in the following termed VPDPR, was found to decrease food intake in rats. The human procolipase activation peptide with the sequence Ala-Pro-Gly-Pro-Arg (APGPR) had no effect on food intake in rats, nor the trypsinogen activation peptide with the sequence Phe-Pro-Val-Asp-Asp-Asp-Asp-Lys (FPVDDDDK). Procolipase added to standard pellets decreased the daily food intake in rats, whereas colipase added to pellets had no effect.

Pancreatic amylase, chymotrypsinogen, lipase and colipase were assayed, at intervals, in rats from day 16 of fetal life until weaning. In the fetus, amylase and chymotrypsinogen accumulated regularly, in parallel, until birth. Lipase and colipase accumulation slowed down between day 20 and birth. The ratio of colipase to lipase was extremely high (9.5) and decreased until weaning towards adult values. Enzyme contents of the pancreas were depleted after birth and remained low until day 14. Intestinal concentrations were equally low, showing that pancreatic depletion was not due to hypersecretion. Protein synthesis was very active, intermediate between that of the fetus and of the adult. It is concluded that in the early suckling phase the proteins synthesized are mainly constitutive and not enzymatic. Starvation followed by refeeding showed that secretion sensitivity to nutritional stimulation only appears at 14 days. During the suckling period amylase concentrations decreased, evidencing a degree of nutritional sensitivity to the low level of carbohydrate in the diet. The productive capacity for lipase underwent a slow maturation which was not even complete at weaning, since concentrations had not yet reached adult level despite the high fat content of milk. This was in part compensated for by the high proportion of colipase but shows that lipase was not adaptative during this phase and that pancreatic lipase can hardly account for lipid digestion before weaning.

The effects of bile salts and colipase on the adsorption of lipase at an interface were studied by hydrophobic affinity chromatography on phenyl- and octyl-Sepharose. In the absence of bile salts, lipase or colipase binds separately to the gel. This is unchanged in the presence of adsorbed bile salts, when one bile salt molecule is associated per hydrophobic ligand. The same data are obtained in the presence of monomeric bile salt solutions. In contrast, lipase adsorption is totally prevented in a micellar bile salt solution. These results favor the idea that the formation of a lipase-bile salt complex in solution is responsible for the lack of interfacial lipase adsorption.

A new automated potentiometric method for the determination of colipase was developed, taking advantage of the reactivation of purified lipase, in the presence of bile salt and at pH 6.5. High-fat and high-starch diets induced an opposite regulation of lipase and amylase in the rat pancreas. At the same time, the level of colipase was not influenced by nutrition. During fasting and in alloxan diabetes, the specific activity of lipase almost doubled, that of amylase decreased sharply, and colipase was not affected in the rat pancreas. In obese-hyperglycemic mice, suffering from obesity, hyperinsulinism, and moderate diabetes, there was also no regulation of pancreatic colipase. Thus, at variance with a number of hydrolases, there was no dietary or hormonal adaptation of colipase. However, this was probably without any bearing on intraluminal lipolysis. Indeed, comparison of lipase and colipase activities in pancreas and in small intestine suggests that colipase concentration is not a limiting factor of intraluminal lipolysis. The molecular mechanism of this assumption is discussed on the basis of in vitro studies.