We have shown that non-pancreatic lipases account for the digestion of 20-40% of dietary fat, and that their activity is probably not confined only to the stomach, but may continue in the small intestine. Furthermore, whereas in the rat, lingual lipase is the only non-pancreatic digestive lipase, in man fat digestion in the stomach may be catalyzed by two enzymes, lingual and gastric lipases. Our studies also show that gastric lipase is present in several other species (dog, guinea pig, baboon) and that is the only non-pancreatic digestive lipase in the rabbit. Therefore, we shall investigate the following the human subjects: 1. The characteristics of purified human lingual and gastric lipases. 2. The quantitative contribution of these two enzymes to intragastric lipolytic activity in the newborn premature and full term infant. 3. The effect of sucking on the quantitative contribution of the two enzymes to the lipolytic activity present in the stomach. The animal models for these studies will be the developing rabbit and dog, species with only or high activity of gastric lapase, respectively. Furthermore feeding patterns, milk fat composition and lipase activity differ in these two species in a way that can provide the data necessary to evaluate the role of lingual and gastric lipases in the fat digestion of formula or breast fed preterm infants. We will investigate: 1. The developmental profile of gastric lipase in the suckling rabbit and of gastric and lingual lipases in the suckling puppy. 2. Detailed characterization of gastric lipase during the developmental period: substrate specificity, stability to conditions prevailing in the stomach (low pH, pepsin) and small intestine (bile salts, proteolytic enzymes). 3. The cellular source of gastric lipase: are lipase and pepsin, the two digestive enzymes secreted by the gastric mucosa, secreted by the same cell type? 4. Quantitation of in vivo lipolysis and fat absorption in the newborn and the contribution of non-pancreatic lipases to this process.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD010823-09
Application #
3311415
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1981-07-01
Project End
1991-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
9
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Georgetown University
Department
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
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Kirk, C L; Iverson, S J; Hamosh, M (1991) Lipase and pepsin activities in the stomach mucosa of the suckling dog. Biol Neonate 59:78-85
Hamosh, M (1991) Free fatty acids and monoglycerides: anti-infective agents produced during the digestion of milk fat by the newborn. Adv Exp Med Biol 310:151-8
Hamosh, M; Mehta, N R; Fink, C S et al. (1991) Fat absorption in premature infants: medium-chain triglycerides and long-chain triglycerides are absorbed from formula at similar rates. J Pediatr Gastroenterol Nutr 13:143-9
Iverson, S J; Kirk, C L; Hamosh, M et al. (1991) Milk lipid digestion in the neonatal dog: the combined actions of gastric and bile salt stimulated lipases. Biochim Biophys Acta 1083:109-19
DiPalma, J; Kirk, C L; Hamosh, M et al. (1991) Lipase and pepsin activity in the gastric mucosa of infants, children, and adults. Gastroenterology 101:116-21

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