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Dietary fats rich in saturated fatty acids (12∶0, 14∶0, and 16∶0) enhance gallstone formation relative to monounsaturated fat (18∶1) in cholesterol-fed hamsters

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Lipids

Abstract

To test the possibility that dietary palmitic acid (16∶0) may be lithogenic, different fats were blended to exchange 18∶1 in olive oil with either 16∶0 in palm stearin, 12∶0+14∶0 in coconut oil, or 14∶0+16∶0 in butterfat. Dietary 18∶2 was held constant at 1.2% energy (en) (with extra safflower oil as needed) in these four purified diets containing low fat (11% of total energy) and 0.4% cholesterol. A fifth, high-fat diet provided 40% of the total energy as the 16∶0-rich blend. All hamsters fed the low-fat, 16∶0-rich blend for six weeks developed cholesterol gallstones (8/8). Although the gallstone incidence was lower for the 12∶0+14∶0-rich diet (5/8), the severity of stone formation in affected hamsters was equal to that in the low-fat, 16∶0-rich group. Mucin accumulation in gallbladder bile was often associated with cholesterol gallstones in diets containing 16∶0, but was minimal in 18∶1-rich and 12∶0+14∶0-rich groups. Neither the lithogenic index (all>1.0), plasma lipids, nor liver cholesterol was a selective predictor of stone formation. The high-fat, 16∶0-rich diet actually decreased cholesterol stone incidence (3/8) and severity, but yielded a high incidence of pigment stones (5/8). Thus, saturated fat and 16∶0per se were not responsible for the exaggerated lithogenesis. Because the antilithogenic 18∶1-rich diet also normalized the 18∶2 intake (1.2% en) relative to previous butter diets (0.3% en), the potential importance of essential fatty acids (EFA) deficiency in the model was tested in a second study by feeding graded amounts of 18∶2 (0.3, 0.6, 0.9, and 1.2% en) as safflower oil in four low-fat, butter-rich diets (11% en as fat) without alleviating gallstone incidence or severity. These studies indicate that substitution of 18∶1 for saturated fatty acids in low-fat diets reduces gallstone formation without affecting the lithogenic index. Furthermore, intake of 18∶2 at or below the EFA requirement does not appear to be a major factor in this model.

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Abbreviations

ACAT:

acyl cholesterol acyl transferase

ANOVA:

analysis of variance

apo B:

apolipoprotein B

apo E:

apolipoprotein E

CE:

cholesteryl ester

EFA:

essential fatty acid

en:

energy

HDL:

high-density lipoprotein

HI:

hydrophobicity index

HPLC:

high-performance liquid chromatography

LDL:

low-density lipoprotein

LDLi:

low density lipoprotein receptor

LI:

lithogenic index

PUFA:

polyunsaturated fatty acids

TC:

total cholesterol

References

  1. Hayes, K.C., Livingston, A., and Trautwein, E.A. (1992) “Dietary Impact on Biliary Lipids and Gallstones,”Annu. Rev. Nutr. 12, 299–326.

    Article  PubMed  CAS  Google Scholar 

  2. Liepa, G., Gorman, M.A., and Duffy, A.M. (1988) “The Use of Animals in Studying the Effects of Diet on Gallstone Formation,” inComparative Animal Nutrition (Beynen, A.C., and West, C.E., eds.) Vol. 6, pp. 149–173, S. Karger, Basel, Switzerland.

    Google Scholar 

  3. Tanimura, H. (1965) “Experimental Studies on the Etiology of Cholelithiasis,”Arch. Jpn. Chir. 34, 1160–1179.

    Google Scholar 

  4. Wheeler, H.O. (1973) “Biliary Excretion of Bile Acids, Lecithin, and Cholesterol in Hamsters with Gallstones,”Gastroenterol. 65, 92–103.

    CAS  Google Scholar 

  5. Bennion, L.J., and Grundy, S.M. (1978) “Risk Factors for the Development of Cholelithiasis in Man,”New Engl. J. Med. 299, 1221–1227.

    Article  PubMed  CAS  Google Scholar 

  6. Maclure, K.M., Hayes, K.C., Colditz, G.A., Stampfer, M.J., and Willett, W.C. (1990) “Dietary Predictors of Symptom-associated Gallstones in Middle-aged Women,”Am. J. Clin. Nutr. 52, 916–922.

    PubMed  CAS  Google Scholar 

  7. Trautwein, E.A., Liang, J., and Hayes, K.C. (1993) “Cholesterol Gallstone Induction in Hamsters Reflects Strain Differences in Plasma Lipoproteins and Bile Acid Profiles,”Lipids 28, 305–312.

    PubMed  CAS  Google Scholar 

  8. Cohen, B.I., Mosbach, E.H., Ayyad, N., Miki, S., and McSherry, C.K. (1992) “Dietary Fat and Fatty Acids Modulate Cholesterol Cholelithiasis in the Hamster,”Lipids 27, 526–532.

    PubMed  CAS  Google Scholar 

  9. Shioda, R. (1965) “Experimental Studies or Gallstone Formation,”Arch. Jpn. Chir. 34, 571–585.

    CAS  Google Scholar 

  10. Dam, H. (1971) “Determinants of Cholesterol Cholelithiasis in Man and Animals,”Am. J. Med. 51, 596–613.

    Article  PubMed  CAS  Google Scholar 

  11. Weingard, K.W., and Daggy, B.P. (1990) “Quantification of HDL Cholesterol in Plasma from Hamsters by Differential Precipitation,”Clin. Chem. 36, 575.

    Google Scholar 

  12. Hayes, K.C., Stephan, Z.F., Pronczuk, A., Lindsey, S., and Verdon, C. (1989) “Lactose Protects Against Estrogen-induced Pigment Gallstones in Hamsters Fed Nutritionally Adequate Purified Diets,”J. Nutr. 119, 1726–1736.

    PubMed  CAS  Google Scholar 

  13. Folch, J., Lees, M., and Stanley, G.H.S. (1957) “A Simple Method for the Isolation and Purification of Total Lipids from Animal Tissue,”J. Biol. Chem. 226, 497–509.

    PubMed  CAS  Google Scholar 

  14. Rossi, S.S., Converse, J.L., and Hofmann, A.F. (1987) “High-Pressure Liquid Chromatographic Analysis of Conjugated Bile Acids in Human Bile: Simultaneous Resolution of Sulfated and Unsulfated Lithocholyl Amidates and The Commonly Conjugated Bile Acids,”J. Lipid Res. 28, 589–595.

    PubMed  CAS  Google Scholar 

  15. Trautwein, E.A., Liang, J., and Hayes, K.C. (1993) “Plasma Lipoproteins, Biliary Lipids and Bile Acid Profile Differ in Various Strains of Syrian Hamsters,”Comp. Biochem. Physiol. 104A, 829–835.

    Article  CAS  Google Scholar 

  16. Carey, M.C., and Small, D.M. (1978) “The Physical Chemistry of Cholesterol Solubility in Bile: Relationship to Gallstone Formation and Dissolution in Man,”J. Clin. Invest. 61, 998–1026.

    PubMed  CAS  Google Scholar 

  17. Heuman, D.M. (1989) “Quantitative Estimation of the Hydrophilic-Hydrophobic Balance of Mixed Bile Salt Solutions,”J. Lipid Res. 30, 719–730.

    PubMed  CAS  Google Scholar 

  18. Kim, J.C., and Chung, T.H. (1984) “Direct Determination of the Free Cholesterol and Individual Cholesteryl Esters in Serum by HPLC,”Korean J. Biochem. 16, 69–77.

    CAS  Google Scholar 

  19. Suckling, K.E., Benson, G.M., Bond, B., Gee, A., Glen, A., Haynes, C., and Jackson, B. (1991) “Cholesterol Lowering and Bile Acid Excretion in the Hamster with Cholestyramine Treatment,”Atherosclerosis 89, 183–190.

    Article  PubMed  CAS  Google Scholar 

  20. Cohen, B.I., Matoba, N., Mosbach, E.H., and McSherry, C. (1989) “Dietary Induction of Cholesterol Gallstones in Hamsters from Three Different Sources,”Lipids 24, 151–156.

    Article  PubMed  CAS  Google Scholar 

  21. Hayes, K.C., Khosla, P., Kaiser, A., Yeghiazarians, V., and Pronczuk, A. (1992) “Dietary Fat and Cholesterol Modulate the Plasma Lipoprotein Distribution and Production of Pigment or Cholesterol Gallstones in Hamsters,”J. Nutr. 122, 374–384.

    PubMed  CAS  Google Scholar 

  22. Ayyad, N., Cohen, B.I., Mosbach, E.H., and Miki, S. (1992) “Palmitic Acid Enhances Cholesterol Gallstone Incidence in Sasco Hamsters Fed Cholesterol Enriched Diets,”Lipids 27, 993–998.

    PubMed  CAS  Google Scholar 

  23. Carey, M.C. (1989) “Formation of Cholesterol Gallstones: the New Paradigms,” inTrends in Bile Acid Research (Paumgartner, G., Stiehl, A., and Gerok, W., eds.), pp. 259–281, Kluwer Academic Publishers, Dordricht/Boston/London.

    Google Scholar 

  24. Spady, D.K., Woollett, L.A., and Dietschy, J.M. (1993) “Regulation of Plasma LDL-Cholesterol Levels by Dietary Cholesterol and Fatty Acids,”Ann. Rev. Nutr. 13, 355–381.

    Article  CAS  Google Scholar 

  25. Ginsberg, R.L., Duane, W.C., and Flock, E.V. (1977) “Hepatic 3-Hydroxy-3-Methylglutaryl CoA Reductase Activity in Hamsters on a Lithogenic Diet,”J. Lab. Clin. Med. 89, 928–936.

    PubMed  CAS  Google Scholar 

  26. Ochoa, B., Gee, A., Jackson, B., and Suckling, K.E. (1990) “Regulation of Cholesteryl Ester Metabolism in the Hamster Liver,”Biochim. Biophys. Acta 1044, 133–138.

    PubMed  CAS  Google Scholar 

  27. Daumerie, C.M., Woollett, L.A., and Dietschy, J.M. (1992) “Fatty Acids Regulate Hepatic Low Density Lipoprotein Receptor Activity Through Redistribution of Intracellular Cholesterol Pools,”Proc. Natl. Acad. Sci. USA 89, 10797–10801.

    Article  PubMed  CAS  Google Scholar 

  28. Woollett, L.A., Spady, D.K., and Dietschy, J.M. (1992) “Saturated and Unsaturated Fatty Acids Independently Regulate Low Density Lipoprotein Receptor Activity and Production Rate,”J. Lipid Res. 33, 77–88.

    PubMed  CAS  Google Scholar 

  29. Spady, D.K., and Dietschy, J.M. (1988) “Interaction of Dietary Cholesterol and Triglycerides in the Regulation of Hepatic LDL Transport in the Hamster,”J. Clin. Invest. 81, 300–309.

    Article  PubMed  CAS  Google Scholar 

  30. Turley, S.D., Spady, D.K., and Dietschy, J.M. (1983) “Alteration of the Degree of Biliary Cholesterol Saturation in the Hamster and Rat by Manipulation of the Pools of Preformed and Newly Synthesized Cholesterol,”Gastroenterol. 84, 253–264.

    CAS  Google Scholar 

  31. Spady, D.K., Turley, S.D., and Dietschy, J.M. (1983) “Dissociation of Hepatic Cholesterol Synthesis from Hepatic LDL Uptake Ad Biliary Cholesterol Saturation in Female and Male Hamsters of Different Ages,”Biochim. Biophys. Acta 753, 381–392.

    PubMed  CAS  Google Scholar 

  32. Gustafsson, B.F., Einarsson, K., and Gustafsson, J.A. (1975) “Influence of Cholesterol Feeding on Liver Microsomal Metabolism of Steroids and Bile Acids in Conventional and Germ-free Rats,”J. Biol. Chem. 250, 8496–8502.

    PubMed  CAS  Google Scholar 

  33. Trautwein, E.A., Siddiqui, A., and Hayes, K.C. (1993) “Modelling Plasma Lipoprotein-bile Lipid Relationships: Differential Impact of Psyllium and Cholestyramine in Hamsters Fed a Lithogenic Diet,”Metabolism 42, 1531–1540.

    Article  PubMed  CAS  Google Scholar 

  34. Singhal, A.K., Finver-Sadowsky, J., McSherry, C.K., and Mosbach, E.H. (1983) “Effect of Cholesterol and Bile Acids on the Regulation of Cholesterol Metabolism in Hamster”,Biochim. Biophys. Acta 752, 214–222.

    PubMed  CAS  Google Scholar 

  35. Kuroki, S., Muramoto, S., Kuramoto, T., and Hoshita, T. (1983) “Effect of Feeding Cholesterol and Sitosterol on Hepatic Steroid 12 α-Hydroxylase Activity in Female Hamsters,”J. Pharm. Dyn. 6, 551–557.

    CAS  Google Scholar 

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Author notes

  1. Elke A. Trautwein

    Present address: Institute of Human Nutrition and Food Science, University of Kiel, 24105, Kiel, Germany

Authors and Affiliations

  1. Foster Biomedical Research Laboratory, Brandeis University, 02254, Waltham, Massachusetts

    Satya S. Jonnalagadda, Elke A. Trautwein & K. C. Hayes

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  2. Elke A. Trautwein
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Jonnalagadda, S.S., Trautwein, E.A. & Hayes, K.C. Dietary fats rich in saturated fatty acids (12∶0, 14∶0, and 16∶0) enhance gallstone formation relative to monounsaturated fat (18∶1) in cholesterol-fed hamsters. Lipids 30, 415–424 (1995). https://doi.org/10.1007/BF02536299

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  • DOI: https://doi.org/10.1007/BF02536299

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