Abstract
We tested the hypothesis that breast-vs. formula-feeding differentially affects the enzymatic activity of three sterol hydroxylases critical in the initial steps of bile acid formation. Thirty baboons were either breast-fed or formula-fed for the first 14 wk of life before weaning to baboon chow. At 14 and 34 wk of age, liver biopsies were assayed for cholesterol 7α-hydroxylase (CYP7A1), 27-hydroxycholesterol-7α-hydroxylase (CYP7B1), and cholesterol 27-hydroxylase (CYP27A1). We also determined the kinetics of 3H-27-hydroxycholesterol (27-OHC) turnover in vivo at both ages. At 14 wk of age, hepatic CYP7A1 activity was low but sevenfold higher among formula-fed vs. breast-fed baboons. By 34 wk, CYP7A1 activity had increased nearly 10-fold in both infant diet groups, and the sevenfold difference in CYP7A1 between previously breast-and formula-fed animals persisted. There were no differences in CYP7B1 activities between infant diet groups at either 14 or 34 wk of age although the activity increased in both groups by about 50% from 14 to 34 wk. CYP27A1 activity also increased between 14 and 34 wk of age, and, compared with CYP7A1, relatively small differences in CYP27A1 activity due to infant diet were observed at each age. Plasma 27-OHC turnover had a half-time of 2–4 min. We had previously reported that after weaning, the total bile acid synthesis rate was higher among baboons that were formula-fed than among breast-fed animals. The present results suggest that this difference is most likely due to significantly higher CYP7A1 activity among formula-fed vs. breast-fed animals.
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Abbreviations
- 27-OHC:
-
27-hydroxycholesterol
- CYP7A1:
-
cholesterol 7α-hydroxylase
- CYP7B1:
-
27-hydroxycholesterol-7α-hydroxylase
- CYP27A1:
-
cholesterol 27-hydroxylase
- MTBE:
-
methyl t-butyl ether
- SFBR:
-
Southwest Foundation for Biomedical Research
- SPE:
-
solid-phase extraction
- StAR:
-
steroidogenic acute regulatory
- STE buffer:
-
0.25 M sucrose, 5 mM Tris, and 1 mM EGTA, pH 7.2
- TMS:
-
trimethylsilyl
References
Mott, G.E., Jackson, E.M., DeLallo, L., Lewis, D.S., and McMahan, C.A. (1995) Differences in Cholesterol Metabolism in Juvenile Baboons Are Programmed by Breast-Versus Formula-Feeding, J. Lipid Res. 36, 299–307.
Lewis, D.S., Mott, G.E., McMahan, C.A., Masoro, E.J., Carey, K.D., and McGill, H.C., Jr. (1988) Deferred Effects of Preweaning Diet on Atherosclerosis in Adolescent Baboons, Arteriosclerosis 8, 274–280.
Mott, G.E., Jackson, E.M., McMahan, C.A., Farley, C.M., and McGill, H.C., Jr. (1985) Cholesterol Metabolism in Juvenile Baboons: Influence of Infant and Juvenile Diets, Arteriosclerosis 5, 347–354.
Mott, G.E., Jackson, E.M., McMahan, C.A., and McGill, H.C., Jr. (1990) Cholesterol Metabolism in Adult Baboons Is Influenced by Infant Diet, J. Nutr. 120, 243–251.
Jackson, E.M., Lewis, D.S., McMahan, C.A., and Mott, G.E. (1993) Preweaning Diet Affects Bile Lipid Composition and Bile Acid Kinetics in Infant Baboons, J. Nutr. 123, 1471–1479.
Vlahcevic, Z.R., Pandak, W.M., and Stravitz, R.T. (1999) Regulation of Bile Acid Biosynthesis, Gastroenterol. Clin. North Am. 28, 1–25.
Duane, W.C., and Javitt, N.B. (2002) Conversion of 7α-Hydroxycholesterol to Bile Acid in Human Subjects: Is There an Alternate Pathway Favoring Cholic Acid Synthesis?, J. Lab. Clin. Med. 139, 109–115.
Nguyen, L.B., Xu, G., Shefer, S., Tint, G.S., Batta, A., and Salen, G. (1999) Comparative Regulation of Hepatic Sterol 27-Hydroxylase and Cholesterol 7α-Hydroxylase Activities in the Rat, Guinea Pig, and Rabbit: Effects of Cholesterol and Bile Acids, Metabolism 48, 1542–1548.
Rudel, L.L., Deckelman, C., Wilson, M., Scobey, M., and Anderson, R. (1994) Dietary Cholesterol and Downregulation of Cholesterol 7α-Hydroxylase and Cholesterol Absorption in African Green Monkeys, J. Clin. Invest. 93, 2463–2472.
Duane, W.C. (1993) Effects of Lovastatin and Dietary Cholesterol on Sterol Homeostasis in Healthy Human Subjects, J. Clin. Invest. 92, 911–918.
Pandak, W.M., Ren, S., Marques, D., Hall, E., Redford, K., Mallonee, D., Bohdan, P., Heuman, D., Gil, G., and Hylemon, P. (2002) Transport of Cholesterol into Mitochondria Is Rate-Limiting for Bile Acid Synthesis via the Alternative Pathway in Primary Rat Hepatocytes, J. Biol. Chem. 277, 48158–48164.
Mott, G.E., Lewis, D.S., and McMahan, C.A. (1993) Infant Diet Affects Serum Lipoprotein Concentrations and Cholesterol Esterifying Enzymes in Baboons, J. Nutr. 123, 155–163.
Lascelles, C.V., and Quant, P.A. (1997) Investigation of Human Hepatic Mitochondrial 3-Hydroxy-3-methylglutaryl-coenzyme A Synthase in Postmortem or Biopsy Tissue, Clin. Chim. Acta 260, 85–96.
Winegar, D.A., Salisbury, J.A., Sundseth, S.S., and Hawke, R.L. (1996) Effects of Cyclosporin on Cholesterol 27-Hydroxylation and LDL Receptor Activity in HepG2 Cells, J. Lipid. Res. 37, 179–191.
Reiss, A.B., Martin, K.O., Javitt, N.B., Martin, D.W., Grossi, E.A., and Galloway, A.C. (1994) Sterol 27-Hydroxylase: High Levels of Activity in Vascular Endothelium, J. Lipid Res. 35, 1027–1030.
Martin, K.O., Budai, K., and Javitt, N.R. (1993) Cholesterol and 27-Hydroxycholesterol 7α-Hydroxylation: Evidence for Two Different Enzymes, J. Lipid Res. 34, 581–588.
Li, S., Pang, J., Wilson, W.K., and Schroepfer, G.J., Jr. (1999) Sterol Synthesis. Preparation and Characterization of Fluorinated and Deuterated Analogs of Oxygenated Derivatives of Cholesterol, Chem. Phys. Lipids 99, 33–71.
Ni, Y., Kisic, A., Wilson, W.K., and Schroepfer, G.J., Jr. (1994) Inhibitors of Sterol Synthesis Tritium-Labeled 27-Hydroxycholesterol of High Specific Activity from a Byproduct of the Clemmensen Reduction of Diosgenin, J. Lipid Res. 35, 546–559.
Li, S., Pang, J., Jackson, E.M., Wilson, W.K., Mott, G.E., and Schroepfer, G.J., Jr. (2000) Kinetics and Plasma Concentrations of 27-Hydroxycholesterol in Baboons, Biochim. Biophys. Acta 1485, 173–184.
Bligh, E.G., and Dyer, W.J. (1959) A Rapid Method of Total Lipid Extraction and Purification, Can. J. Biochem. Physiol. 37, 911–917.
Setchell, K.D.R., Schwarz, M., O’Connell, N.C., Lund, E.G., Davis, D.L., Lathe, R., Thompson, H.R., Tyson, R.W., Sokol, R.J., and Russell, D.W. (1998) Identification of a New Inborn Error in Bile Acid Synthesis: Mutation of the Oxysterol 7α-Hydroxylase Gene Causes Severe Neonatal Liver Disease, J. Clin. Invest. 102, 1690–1703.
Setchell, K.D.R., Dumaswala, R., Colombo, C., and Ronchi, M. (1988) Hepatic Bile Acid Metabolism During Early Development Revealed from the Analysis of Human Fetal Gallbladder Bile, J. Biol. Chem. 263, 16637–16644.
Schwarz, M., Lund, E.G., Setchell, K.D.R., Kayden, H.J., Zerwekh, J.E., Bjorkhem, I., Herz, J., and Russell, D.W. (1996) Disruption of Cholesterol 7α-Hydroxylase Gene in Mice II, J. Biol. Chem. 271, 18024–18031.
Ishibashi, S., Schwarz, M., Frykman, P.K., Herz, J., and Russell, D.W. (1996) Disruption of Cholesterol 7α-Hydroxylase Gene in Mice. I., J. Biol. Chem. 271, 18017–18023.
Norlin, M. (2002) Expression of Key Enzymes in Bile Acid Biosynthesis During Development: CYP7B1-Mediated Activities Show Tissue-Specific Differences, J. Lipid Res. 43:721–731.
Lewis, D.S., Oren, S., Wang, X., Moyer, M.L., Beitz, D.C., Knight, T.J., and Mott, G.E. (2000) Developmental Changes in Cholesterol 7α-and 27-Hydroxylases in the Piglet, J. Anim. Sci. 78, 943–951.
Norlin, M., Andersson, U., Bjorkhem, I., and Wikvall, K. (2000) Oxysterol 7α-Hydroxylase Activity by Cholesterol 7α-Hydroxylase (CYP7A), J. Biol. Chem. 275, 34046–34053.
Schroepfer, G.J., Jr. (2000) Oxysterols: Modulators of Cholesterol Metabolism and Other Processes, Physiol. Rev. 80, 361–554.
Bjorkhem, I., Araya, Z., Rudling, M., Angelin, B., Einarsson, C., and Wikvall, K. (2002) Differences in the Regulation of the Classical and the Alternative Pathways for Bile Acid Synthesis in Human Liver, J. Biol. Chem. 277, 26804–26807.
Javitt, N.B. (2002) 25R, 26-Hydroxycholesterol Revisited: Synthesis, Metabolism, and Biologic Roles, J. Lipid Res. 43, 665–670.
Sugawara, T., Lin, D., Holt, J.A., Martin, K.O., Javitt, N.B., Miller, W.L., and Strauss, J.F., III (1995) Structure of the Human Steroidogenic Acute Regulatory Protein (StAR) Gene: StAR Stimulates Mitochondrial Cholesterol 27-Hydroxylase Activity, Biochemistry 34, 12506–12512.
Lewis, D.S., McMahan, C.A., and Mott, G.E. (1993) Breast-Feeding and Formula-Feeding Affect Differently Plasma Thyroid Hormone Concentrations in Infant Baboons, Biol Neonate 63, 327–335.
Mott, G.E., Lewis, D.S., Jackson, E.M., and McMahan, C.A. (1996) Preweaning Diet Programs Postweaning Plasma Thyroxine Concentrations in Baboons, Proc. Soc. Exp. Biol. Med. 212, 342–348.
Drover, V.A., Wong, N.C., and Agellon, L.B. (2002) A Distinct Thyroid Hormone Response Element Mediates Repression of the Human Cholesterol 7α-Hydroxylase (CYP7A1) Gene Promoter, Mol. Endocrinol. 16, 14–23.
Duane, W.C., and Javitt, N.B. (1999) 27-Hydroxycholesterol: Production Rates in Normal Human Subjects, J. Lipid Res. 40, 1194–1199.
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Mott, G.E., Jackson, E.M., Klein, M.L. et al. Programming of initial steps in bile acid synthesis by breat-feeding vs. Formula-feeding in the baboon. Lipids 38, 1213–1220 (2003). https://doi.org/10.1007/s11745-003-1181-y
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DOI: https://doi.org/10.1007/s11745-003-1181-y