Bo Fredrikzon

Bile salt-stimulated lipase in human milk: evidence of activity in vivo and of a role in the digestion of milk retinol esters.

Summary: Human milk contains an enzyme which, in the presence of certain bile salts, has high lipase and esterase activity. These activities are lost on pasteurization of the milk. Bile salt-stimulated lipase was demonstrated in gastric contents during the first 2 hr after feeding fresh human milk to infants, indicating that it is stable in the stomach and passes with the milk into the duodenum where it is activated by bile salts.When infants were fed test meals of pasteurized human milk both esterase and lipase activities in their duodenal contents fell, presumably because the milk diluted their endogenous enzymes. In contrast, when fresh milk was fed, the esterase activity did not decrease. The difference in esterase activity 1 hr after feeding fresh and pasteurized milk corresponded to the activity in the milk.The bile salt-stimulated lipase of milk but not the pancreatic lipase is inhibited by eserine. After feeding fresh milk a fraction of the lipase activity of duodenal contents was inhibited by eserine; the amount so inhibited corresponded to the activity of the milk. Duodenal contents collected 1 hr after feeding fresh milk were found to hydrolyze retinol palmitate severalfold faster than duodenal contents obtained after feeding pasteurized milk; again the difference corresponded to the activity of the milk fed. It is concluded that the bile salt-stimulated milk lipase is active in the infants intestine and may contribute to the digestion of the milk lipids, particularly the retinol esters.Speculation: The bile salt-stimulated lipase has been found in milk only from primates; it is not present in lower animals. There are few examples of a new enzyme function which appears so late in evolution and an important physiologic role for this lipase is implicated. It may ensure an adequate lipolytic capacity in the intestine under conditions when the infants endogenous enzyme activities are critically low. Since the bile salt-stimulated lipase was found to enhance severalfold the rate at which retinol esters are hydrolyzed by intestinal contents of the newborn, it seems possible that it may considerably enhance the utilization of the retinol esters in milk. These are the main source of vitamin A for the newborn, and must be hydrolyzed before they are absorbed. This vitamin is necessary for normal growth and development but the amounts present in human milk are often barely sufficient to cover the needs of the newborn, particularly when the mother is malnourished. Vitamin A deficiency is common in many nonprivileged societies and a role for the bile salt-stimulated lipase in enhancing its absorption could be of great nutritional significance.

Chronic inflammatory bowel disease in children and adolescents in Sweden

Summary: The incidence and prevalence of chronic inflammatory bowel disease (IBD) in children was established during 1984 and 1985 in a prospective study in Sweden. The patients with IBD were classified as having ulcerative colitis (UC), Crohns disease (CD), probable Crohns disease (PCD), and indeterminate colitis (IC) according to defined histopathologic, endoscopic, and radiologic criteria. The study covered 1.51 million children <16 years of age (93% of all children in Sweden). The incidence of IBD was 5.0 and 4.5 and the prevalence was 17.6 and 18.2 per 100,000 children during the 2 years, respectively. The mean prevalence of UC was 7.5 per 100,000 and of CD + PCD was 6.2 per 100,000. The prevalence of IC was 4.2 per 100,000, which corresponds to 23% of the children with IBD.

Decrease of lipase and esterase activities in intestinal contents of newborn infants during test meals.

Summary: Both lipase and esterase activities were present in intestinal contents of all newborns studied, from the Fist day of life. In adults given a test meal lipase activity increased and esterase activity remained unchanged. In contrast, both activities decreased markedly in infants on feeding. During the digestion of the test meal the lipase activity in intestinal contents of the infants was much lower than in adults (ratio of median values 1:27) and the esterase activity was also several fold lower (ratio of median values 1:4.3).Speculation: Newborn infants often absorb lipids less efficiently than adults. One contributing factor may be that their incompletely developed pancreas responds to feedings with comparatively low outputs of lipolytic enzymes. The newborn may be more dependent than adults on auxiliary sources of lipase activity such as the pharyngeal lipase and/or the bile salt-stimulated lipase in human milk.

Lingual Lipase. an Important Lipase in the Digestion of Dietary Lipids in Cystic Fibrosis

Summary: A convenient lipase assay that discriminates between pancreatic and lingual lipase activities was developed to describe some properties of the triglyceride-hydrolyzing activities of lingual lipase (from von Ebners glands) and pancreatic lipase. Secretion of lingual lipase is stimulated by feeding. Gastric contents collected postyprandially from patients with cystic fibrosis (CF) contained lipase activity which is probably secreted from pharyngeal tissues. Also, duodenal contents from CF patients contained lipase activity with properties very close to those found in gastric contents from CF patients and controls. Apparently, the serous glands responsible for the secretion of lingual lipase is less affected than the exocrine pancrease in this disease.During fat balance experiments, CF patients utilized around 40% of the dietary lipids and more than 50% of milk lipids given as a test meal were hydrolyzed in the duodenum within 2 hr.In these patients with severe pancreatic insufficiency, we suggest that the lingual lipase is responsible for a considerable proportion of triglyceride hydrolysis. This hydrolysis starts in the stomach and continues in duodenum.Speculation: Due to pancreatic insufiiciency, duodenal contents in cystic fibrosis patients is low in proteolytic enzyme activities and also low in pH.Thus, lingual lipase is not rapidly inactivated, and, furthermore, intraluminal pH is near the optimum for catalytic activity of the lingual lipase. This lipase is active in the duodenum where it hydrolyzes a considerable amount of dietary triglycerides. We find it quite probable that the lingual lipase in a similar manner is responsible for a substantial hydrolysis also in healthy subjects, especially in the newborn period where postprandial pancreatic lipase activity is comparatively low (10).

ROLE OF FEEDING ON LIPASE ACTIVITY IN GASTRIC CONTENTS

Abstract. Lipase activity was recorded in gastric contents collected from healthy term and preterm neonates. In contrast to pancreatic lipase activity this lipase activity was higher at pH 5.5 than at pH 8.0 and it was more resistent to acid inactivation. Lipase activity was found in gastric contents from all infants who were regularly fed, but was not present in gastric contents from some infants when collected before regular feeding was established. During test meals lipase activity in gastric contents increased considerably in all infants studied. During such a test meal there was a progressive relative decrease in triglycerides whilst diglycerides showed a relative increase suggesting an active lipolytic process in the stomach. An assay procedure for determination of lipase activity in gastric contents is also described.

Gliadin-specific serum immunoglobulins A, E, G, and M in childhood: relation to small intestine mucosal morphology.

Summary:An enzyme-linked immunosorbent assay technique was developed to determine serum antigliadin antibodies of the IgA, IgE, IgG, and IgM classes. The antibody level of each serum specimen was expressed as an index value, i.e., optical density of test serum/optical density of cutoff, where cutoff was calculated for each immunoglobulin class as the mean + 3 SD for six healthy controls. Indices for each immunoglobulin class were determined in 69 children who were admitted for their first small intestinal mucosal biopsy due to either symptoms of malabsorption compatible with celiac disease, or short stature without other symptoms. Especially raised levels of antigliadin IgA antibodies in serum correlated strongly with villous atrophy and in infants ≤3 years of age were invariably elevated above controls, provided they were on a gluten-containing diet. Raised levels of IgG and IgE antibodies to gluten were often seen in children with normal mucosal morphology, i.e., when symptoms were due to other gastrointestinal disorders than celiac disease. It is concluded that determination of antigliadin IgA antibodies in children ≤3 years is a useful screening test before small intestinal biopsy, especially in children where the indication for biopsy is not otherwise obvious. The method can also be used to assess the results of therapy and, conceivably, compliance.

Lingual lipase. Its role in lipid digestion in infants with low birthweight and/or pancreatic insufficiency.

Fredrikzon, B., Hernell, O. and Bläckberg, L. (Departments of Paediatrics and Physiological Chemistry, University of Umeå, Sweden). Lingual lipase. Its role in lipid digestion in infants with low birthweight and/or pancreatic insufficiency. Acta Paediatr Scand, Suppl. 296: 75, 1982.—At birth both pancreatic lipase and carboxylic ester hydrolase, two important lipolytic enzymes secreted by the pancreas, are present in duodenal contents but the activities of these enzymes are low. Another enzyme of possible importance in lipolysis is the lingual lipase which is secreted from serous glands present at the posterior part of the tongue. The enzyme is present already at birth and has been found in gastric contents from preterm infants in the 34th gestational week. The secretion of lingual lipase is stimulated by feeding and it is resistent against acid inactivation. The activity in gastric contents increases after feeding. This lipase hydrolyzes dietary triglycerides to mainly diglycerides and free fatty acids and may serve as a complement to the poorly developed pancreatic lipase activity. Furthermore, by the formation of polar lipolytic products the digestibility of dietary lipids in the duodenum may increase. Human milk lipase contributes to the lipolysis. It is inactive in the milk but becomes activated by the bile acids in the duodenum. Balance studies in preterm infants have shown that by pasteurization of human milk fat absorption decreases by one third.

GASTROENTEROLOGY: GASTRIC LIPOLYSIS OF HUMAN MILK LIPIDS IN INFANTS WITH PYLORIC STENOSIS

In human infants and puppets a suboptimal concentration of bile acids in the duodenum may interfere with the micelle formation and so the absorption of dietary glycerides. In 1970 Helander and Olivecrona described, in the suckling rat, a lipolytic activity in the stomach. Such an activity has also been found in humans but is thought to be of quantatively minor importance in the normal fat digestion in the adult. We have found in infants a significant hydrolysis of milk triglycerides into diglycerides and free fatty acids to occur already in the stomach. The low pH, the relatively high content of diglycerides in the gastric samples and the nature of the disease of these infants suggests that the hydrolysis was not catalyzed by pancreatic enzymes. The pregastric lipase activity can be of great importance in the postnatal digestion of milk triglycerides in the human infant and to some extent compensate for the poor bile acid concentration found in these infants.