Abstract
During infancy, the basic conditions for digestion of dietary fat differ from later in life. The bile salt–stimulated lipase (BSSL) is an enzyme expressed in the exocrine pancreas and in some species (including human) also in the lactating mammary gland and secreted with the milk. The aim of this study was to compare the ontogeny of four pancreatic lipases [BSSL, pancreatic triglyceride lipase (PL), pancreatic lipase-related protein 2 (PLRP2), and phospholipase A2 (PLA2)] in one species that supplies BSSL with milk (the mouse) and one that does not (the rat). We followed expression of the four pancreatic lipases from postnatal d 1 until after weaning in both species. We found that BSSL and PLRP2, two lipases with broad substrate specificity, dominated. It was not until weaning that significant expression of PL and PLA2 were induced. Thus, BSSL and PLRP2 seem to be responsible for fat digestion as long as milk is the main food. Moreover, the early temporal pattern of BSSL expression differed between species. We speculate that the milk-borne BSSL is able to compensate for a slower ontogeny of pancreatic BSSL expression in the mouse.
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Abbreviations
- BSSL:
-
bile salt-stimulated lipase (EC 3.1.1.3)
- PL:
-
pancreatic triglyceride lipase (EC 3.1.1.3)
- PLA2:
-
phospholipase A2 (EC 3.1.1.4)
- PLRP2:
-
pancreatic lipase-related protein 2 (EC 3.1.1.3)
References
Bernback S, Blackberg L, Hernell O 1990 The complete digestion of human milk triacylglycerol in vitro requires gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase. J Clin Invest 85: 1221–1226
Carriere F, Barrowman JA, Verger R, Laugier R 1993 Secretion and contribution to lipolysis of gastric and pancreatic lipases during a test meal in humans. Gastroenterology 105: 876–888
Carey MC, Hernell O 1992 Digestion and absorption of fat. Semin Gastrointest Dis 3: 189–208
Norman A, Strandvik B, Ojamae O 1972 Bile acids and pancreatic enzymes during absorption in the newborn. Acta Paediatr Scand 61: 571–576
Payne RM, Sims HF, Jennens ML, Lowe ME 1994 Rat pancreatic lipase and two related proteins: enzymatic properties and mRNA expression during development. Am J Physiol 266: G914–G921
Lowe ME, Kaplan MH, Jackson-Grusby L, D'Agostino D, Grusby MJ 1998 Decreased neonatal dietary fat absorption and T cell cytotoxicity in pancreatic lipase-related protein 2-deficient mice. J Biol Chem 273: 31215–31221
Yang Y, Sanchez D, Figarella C, Lowe ME 2000 Discoordinate expression of pancreatic lipase and two related proteins in the human fetal pancreas. Pediatr Res 47: 184–188
Fredrikzon B, Olivecrona T 1978 Decrease of lipase and esterase activities in intestinal contents of newborn infants during test meals. Pediatr Res 12: 631–634
Roussel A, Yang Y, Ferrato F, Verger R, Cambillau C, Lowe M 1998 Structure and activity of rat pancreatic lipase-related protein 2. J Biol Chem 273: 32121–32128
De Caro J, Sias B, Grandval P, Ferrato F, Halimi H, Carriere F, De Caro A 2004 Characterization of pancreatic lipase-related protein 2 isolated from human pancreatic juice. Biochim Biophys Acta 1701: 89–99
Sias B, Ferrato F, Grandval P, Lafont D, Boullanger P, De Caro A, Leboeuf B, Verger R, Carriere F 2004 Human pancreatic lipase-related protein 2 is a galactolipase. Biochemistry 43: 10138–10148
Reboul E, Berton A, Moussa M, Kreuzer C, Crenon I, Borel P 2006 Pancreatic lipase and pancreatic lipase-related protein 2, but not pancreatic lipase-related protein 1, hydrolyze retinyl palmitate in physiological conditions. Biochim Biophys Acta 1761: 4–10
D'Agostino D, Lowe ME 2004 Pancreatic lipase-related protein 2 is the major colipase-dependent pancreatic lipase in suckling mice. J Nutr 134: 132–134
Roussel A, de Caro J, Bezzine S, Gastinel L, de Caro A, Carriere F, Leydier S, Verger R, Cambillau C 1998 Reactivation of the totally inactive pancreatic lipase RP1 by structure-predicted point mutations. Proteins 32: 523–531
Blackberg L, Hernell O 1983 Further characterization of the bile salt-stimulated lipase in human milk. FEBS Lett 157: 337–341
Nyberg L, Farooqi A, Blackberg L, Duan RD, Nilsson A, Hernell O 1998 Digestion of ceramide by human milk bile salt-stimulated lipase. J Pediatr Gastroenterol Nutr 27: 560–567
Hui DY, Howles PN 2002 Carboxyl ester lipase: structure-function relationship and physiological role in lipoprotein metabolism and atherosclerosis. J Lipid Res 43: 2017–2030
Hernell O, Olivecrona T 1974 Human milk lipases. II. Bile salt-stimulated lipase. Biochim Biophys Acta 369: 234–244
Lidmer AS, Kannius M, Lundberg L, Bjursell G, Nilsson J 1995 Molecular cloning and characterization of the mouse carboxyl ester lipase gene and evidence for expression in the lactating mammary gland. Genomics 29: 115–122
Poorkhalkali N, Lidmer AS, Lundberg LG, Dalrymple MA, Gibson Y, Taylor L, Temperley S, Stromqvist M, Helander HF 1998 Bile salt-stimulated lipase (BSSL) distribution in rat, mouse and transgenic mouse expressing human BSSL. Histochem Cell Biol 110: 367–376
Howles PN, Stemmerman GN, Fenoglio-Preiser CM, Hui DY 1999 Carboxyl ester lipase activity in milk prevents fat-derived intestinal injury in neonatal mice. Am J Physiol 277: G653–G661
Laemmli UK 1970 Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685
Hansson L, Blackberg L, Edlund M, Lundberg L, Stromqvist M, Hernell O 1993 Recombinant human milk bile salt-stimulated lipase. Catalytic activity is retained in the absence of glycosylation and the unique proline-rich repeats. J Biol Chem 268: 26692–26698
Blackberg L, Hernell O 1981 The bile-salt-stimulated lipase in human milk. Purification and characterization. Eur J Biochem 116: 221–225
Williamson S, Finucane E, Ellis H, Gamsu HR 1978 Effect of heat treatment of human milk on absorption of nitrogen, fat, sodium, calcium, and phosphorus by preterm infants. Arch Dis Child 53: 555–563
Ricketts J, Brannon PM 1994 Amount and type of dietary fat regulate pancreatic lipase gene expression in rats. J Nutr 124: 1166–1171
Birk RZ, Brannon PM 2004 Regulation of pancreatic lipase by dietary medium chain triglycerides in the weanling rat. Pediatr Res 55: 921–926
Birk RZ, Regan KS, Boyle-Roden E, Brannon PM 2004 Pancreatic lipase and its related protein 2 are regulated by dietary polyunsaturated fat during the postnatal development of rats. Pediatr Res 56: 256–262
Brodt-Eppley J, Hui DY 1994 Dietary regulation of cholesterol esterase mRNA level in rat pancreas. J Lipid Res 35: 27–35
Elinson N, Amichay D, Birk RZ 2006 Leptin directly regulates exocrine pancreas lipase and two related proteins in the rat. Br J Nutr 96: 691–696
Houseknecht KL, McGuire MK, Portocarrero CP, McGuire MA, Beerman K 1997 Leptin is present in human milk and is related to maternal plasma leptin concentration and adiposity. Biochem Biophys Res Commun 240: 742–747
Savino F, Fissore MF, Grassino EC, Nanni GE, Oggero R, Silvestro L 2005 Ghrelin, leptin and IGF-I levels in breast-fed and formula-fed infants in the first years of life. Acta Paediatr 94: 531–537
Savino F, Liguori SA, Lupica MM, Fissore MF, Oggero R 2006 Leptin levels in breast-fed infants. Clin Endocrinol (Oxf) 64: 597–598
Blackberg L, Hernell O, Olivecrona T 1981 Hydrolysis of human milk fat globules by pancreatic lipase: role of colipase, phospholipase A2, and bile salts. J Clin Invest 67: 1748–1752
Bernback S, Blackberg L, Hernell O 1989 Fatty acids generated by gastric lipase promote human milk triacylglycerol digestion by pancreatic colipase-dependent lipase. Biochim Biophys Acta 1001: 286–293
Huggins KW, Camarota LM, Howles PN, Hui DY 2003 Pancreatic triglyceride lipase deficiency minimally affects dietary fat absorption but dramatically decreases dietary cholesterol absorption in mice. J Biol Chem 278: 42899–42905
Richmond BL, Boileau AC, Zheng S, Huggins KW, Granholm NA, Tso P, Hui DY 2001 Compensatory phospholipid digestion is required for cholesterol absorption in pancreatic phospholipase A(2)-deficient mice. Gastroenterology 120: 1193–1202
Howles PN, Carter CP, Hui DY 1996 Dietary free and esterified cholesterol absorption in cholesterol esterase (bile salt-stimulated lipase) gene-targeted mice. J Biol Chem 271: 7196–7202
Falt H, Hernell O, Blackberg L 2002 Does bile salt-stimulated lipase affect cholesterol uptake when bound to rat intestinal mucosa in vitro?. Pediatr Res 52: 509–515
Wong WW, Hachey DL, Insull W, Opekun AR, Klein PD 1993 Effect of dietary cholesterol on cholesterol synthesis in breast-fed and formula-fed infants. J Lipid Res 34: 1403–1411
Bayley TM, Alasmi M, Thorkelson T, Krug-Wispe S, Jones PJ, Bulani JL, Tsang RC 1998 Influence of formula versus breast milk on cholesterol synthesis rates in four-month-old infants. Pediatr Res 44: 60–67
Singhal A, Cole TJ, Fewtrell M, Lucas A 2004 Breastmilk feeding and lipoprotein profile in adolescents born preterm: follow-up of a prospective randomised study. Lancet 363: 1571–1578
Acknowledgements
The authors thank Eva-Lotta Vestman and Yvonne Andersson for excellent technical assistance. We are grateful to Assistant Professor Lars Bläckberg for his interest in the work and for fruitful discussions.
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This work was supported by grants from the Swedish Research Council, Medicine, Her Royal Highness the Crown Princess Lovisa's Society for Pediatric Research/Axel Thielman's Memorial Fund, Västerbotten County Council (ALF), Oskarfonden and Biovitrum AB.
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Li, X., Lindquist, S., Lowe, M. et al. Bile Salt–Stimulated Lipase and Pancreatic Lipase-Related Protein 2 Are the Dominating Lipases in Neonatal Fat Digestion in Mice and Rats. Pediatr Res 62, 537–541 (2007). https://doi.org/10.1203/PDR.0b013e3181559e75
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DOI: https://doi.org/10.1203/PDR.0b013e3181559e75
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