Abstract
Utilization of stearate as compared to various saturated fatty acids for cholesterol and lipid synthesis and β-oxidation was determined in primary culture of rat hepatocytes. At 0.5 mmol/L in the medium, stearate (18:0) adequately solubilized by albumin was less inhibitory to cholesterol synthesis from [2-14C] acetate than myristate (14:0) and palmitate (16:0) (68% vs. 91 and 88% inhibition, respectively). The rate of incorporation into cholesterol from [1-14C] stearate (3.0±0.6 nmol/mg protein/4 h) was 37-, 1.8-, and 7.8-fold of that from myristate, palmitate, and oleate, respectively. Conversely, the rate of [1-14C] stearate incorporation into total glycerolipids was 88–90% lower than that of labeled palmitate, myristate, and oleate. The rate of [1-14C] stearate incorporation into triacylglycerol (3.6±0.4 nmol/mg protein/4 h) was 6–8% of that from myristate, palmitate, oleate, and linoleate. The rate of stearate incorporation into phospholipids was the lowest among tested fatty acids, whereas the rate of mono- and diacylglycerol synthesis was the highest with stearate treatment. The rate of β-oxidation as measured by CO2 and acid soluble metabolite production was also the lowest with [1-14C] stearate treatment at 22.7 nmol/mg protein/4 h, which was 35–40% of those from other [1-14C] labeled fatty acids. A greater proportion of stearate than other fatty acids taken up by the hepatocytes remained free and was not metabolized. Clearly, stearate as compared to shorter-chain saturated fatty acids was less efficiently oxidized and esterified to triacylglycerol in cultured rat hepatocytes.
Similar content being viewed by others
Abbreviations
- ASM:
-
acid-soluble metabolites
- BSA:
-
bovine serum albumin
- DMEM:
-
Dulbecco's modified Eagle medium
- FBS:
-
fetal bovine serum
- LDL:
-
low density lipoprotein
References
DHHS (U.S. Department of Health and Human Services) (1987) Monthly Vital Statistics Report, Vol. 36: The Advance Report of Final Mortality Statistics, 1985, DHOWS publication no. (PHS)87-1120, National Center for Health and Human Services, Hyattsville, MD, 48 pp.
ACSH (American Council on Science and Health.) (1988) Diet and Coronary Heart Disease, pp. 4–39, ACSH, New York.
Grundy, S.M., and Denke, M.A. (1990) Dietary Influences on Serum Lipids and Lipoproteins,J. Lipid Res. 31, 1149–1172.
Kinsell, L.W., Michaels, G.D., Partridge, F.W., Boling, L.A., Balch, H.E., and Cochrane, G.C. (1953) Effect upon Serum Cholesterol and Phospholipids of Diets Containing Large Amounts of Vegetable Fat,Am. J. Clin. Nutr., 1, 224–231.
Ahrens, E.H., Hirsch, J., Isull, W., Taltas, T.T., Blonstrant, R., and Peterson, M.L. (1957) The Influence of Dietary Fats on Serum-Lipid Levels in Man,Lancet 1, 943–953.
Kannel, W.B., Castelli, W., Gordon, T., and McNamara, D.J. (1971) Serum Cholesterol, Lipoproteins and Risk of Coronary Heart Disease: The Framingham Study,Ann. Intern. Med. 74, 1–12.
Grundy, S.M., (1986) Cholesterol and Coronary Heart Disease. A New Era,J.A.M.A. 256, 2849–2859.
Keys, A., Anderson, J.T., and Grande, F. (1965) Serum Cholesterol Response to Change in the Diet. IV. Particular Saturated Fatty Acids in the Diet,Metabolism 14, 776–787.
Hegsted, M.D., McGandy, R.B., Meyers, M.L., and Stare, F.J. (1965) Quantitative Effects of Dietary Fat on Serum Cholesterol in Man,Am. J. Clin. Nutr. 17, 281–295.
Mattson, F.H., and Grundy, S.M. (1985) Comparison of Effects of Dietary Saturated, Monounsaturated, and Polyunsaturated Fatty Acids on Plasma Lipids and Lipoproteins in Man,J. Lipid. Res. 26, 194–202.
Grundy, S.M., Vega, G.L. (1988) Plasma Cholesterol Responsiveness to Saturated Fatty Acids,Am. J. Clin. Nutr. 47, 822–824.
Bonanome, A., and Grundy, S.M. (1988) Effect of Dietary Stearic Acid on Plasma Cholesterol and Lipoprotein Levels,N. Engl. J. Med. 318, 1244–1248.
Denke, M.A., and Grundy, S.M. (1991) Effects of Fats High in Stearic Acid on Lipid and Lipoprotein Concentrations in Men,Am. J. Clin. Nutr. 54, 1036–1040.
Kris-Etherton, P.M., Derr, J., Mitchell, D.C., Mustard, V.A., Russell, M.E., McDonnell, E.T., Salabsky, D., and Pearson, T.A. (1993) The Role of Fatty Acid Saturation on Plasma Lipids, Lipoproteins and Apolipoproteins: I. Effects of Whole Food Diets High in Cocoa Butter, Olive Oil, Soybean Oil, Dairy Butter, and Milk Chocolate on the Plasma Lipids of Young Men,Metabolism, 42, 121–129.
Monsma, C.C., and Ney, D.M. (1993) Interrelationship of Stearic Acid Content and Triacylglycerol Composition of Lard, Beef Tallow and Cocoa Butter in Rats,Lipids 28, 539–547.
Apgar, J.L., Shively, C.A., and Tarka, Jr., S.M. (1987) Digestibility of Cocoa Butter and Corn Oil and Their Influence on Fatty Acid Distribution in Rats,J. Nutr. 117, 660–665.
Mitchell, D.C., McMahon, K.E., Shively, C.A., Apgar, J.L., and Kris-Etherton, P.M. (1989) Digestibility of Cocoa Butter and Corn Oil in Human Subjects: A Preliminary Study,Am. J. Clin. Nutr. 50, 983–986.
Bergstedt, S.E., Hayashi, H., Kritchevsky, D., and Tso, P. (1990) A Comparison of Absorption of Glycerol Tristearate and Glycerol Trioleate by Rat Small Intestine,Am. J. Physiol. 259, G386-G393.
Woollett, L.A., Spady, D.K., and Dietschy, J.M. (1992) Regulatory Effects of the Saturated Fatty Acids 6:0 Through 18:0 on Hepatic Low Density Lipoprotein Receptor Activity in the Hamster,J. Clin. Invest., 89, 1133–1141.
Bonanome, A., and Grundy, S.M. (1989) Intestinal Absorption of Stearic Acid After Consumption of High Fat Meals in Humans,J. Nutr. 119, 1556–1560.
Bonanome, A., Bennet, M., and Grundy, S.M. (1992) Metabolic Effects of Dietary Stearic Acid in Mice: Changes in the Fatty Acid Composition of Triglycerides and Phospholipids in Various Tissues,Atherosclerosis 94, 119–127.
Berry, M.N., and Friend, D.S. (1969) High-Yield Preparation of Isolated Rat Liver Parenchymal Cells. A Biochemical and Fine Structural Study,J. Cell. Biol. 43, 506–520.
Seglen, P.O. (1973) Preparation of Rat Liver Cells. 3. Enzymatic Requirements for Tissue Dispersion,Exp. Cell Res. 82, 391–398.
Yeh, Y.Y., and Yeh, S.M. (1994) Garlic Reduces Plasma Lipids by Inhibiting Hepatic Cholesterol and Triacylglycerol Synthesis,Lipids 29, 189–193.
Folch, J., Lees, M., and Sloane-Stanley, G.H. (1957) A Simple Method for the Isolation and Purification of Total Lipids from Animal Tissues,J. Biol. Chem., 226, 497–509.
Leveille, G.A., and Yeh, Y.Y. (1972) Influence of Intermittent Fasting or Protein-Free Feeding on Lipid Metabolism in Young Cockerels,J. Nutr. 102, 733–740.
Lowry, O.H., Rosenbrough, N.J., Farr, A.L., and Randle, R.J. (1951) Protein Measurement with Folin Phenol Reagent,J. Biol. Chem., 193, 265–275.
Yeh, Y.Y., Streuli, V.L., and Zee, P. (1977) Relative Utilization of Fatty Acids for Synthesis of Ketone Bodies and Complex Lipids in the Liver of Developing Rats,Lipids 12, 367–374.
Zaleski, J., and Ontko, J.A. (1985) Reciprocal Effects of Energy Utilization on Palmitate Oxidation and Esterification in Hepatocytes of Fed Rats,Biochim. Biophys. Acta 836, 134–142.
Azein, M.J., and Martin, R. (1983) Effect of Genetic Obesity on the Regulation of Hepatic Fatty Acid Metabolism,Am. J. Physiol. 244, R400-R406.
Goodman, D.W. (1958) The Distribution of Fatty Acids Betweenn-Heptane and Aqueous Phosphate Buffer,J. Am. Chem. Soc. 80, 3887–3892.
Goodman, D.W. (1958) The Interaction of Human Serum Albumin with Ion-Chain Fatty Acid Anions,J. Am. Chem. Soc., 80, 3892–3898.
Ott, L. (1984) Multiple Comparisons, inAn Introduction to Statistical Methods and Data Analysis, 2nd edn., pp. 361–387, Duxbery Press, Boston.
Schulz, H. (1994) Regulation of Fatty Acid Oxidation in Heart,J. Nutr. 124, 165–171.
Spady, D.K., Woollett, L.A., and Dietschy, J.M. (1993) Regulation of Plasma LDL-Cholesterol Levels by Dietary Cholesterol and Fatty Acids,Annu. Rev. Nutr. 13, 355–381.
Nestel, P.J., and Steinberg, D. (1963) Fate of Palmitate and of Linoleate Perfused Through the Isolated Rat Liver at High Concentrations,J. Lipid Res. 4, 461–469.
Kohour, M., Kohourova, B., and Heimberg, M. (1971) The Regulation of Hepatic Triglyceride Metabolism by Free Fatty Acids,J. Biol. Chem. 246, 5067–5074.
McGarry, J.D., and Foster, D.W. (1972) Regulation of Ketogenesis and Clinical Aspects of the Ketotic State,Metabolism, 21, 471–489.
Mayes, P.A., and Feltz, J.M. (1967) Regulation of Fat Metabolism of the Liver,Nature 215, 716–718.
Wong, S., Reardon, M., and Nestel, P.J., (1985) Reduced Triglyceride Formation from Long-Chain Polyenoic Fatty Acids in Rat Hepatocytes,Metabolism 34, 900–905.
Wong, S.H., Nestel, P.J., Trimble, R.P., Storer, G.B., Illman, R.J., and Topping D.L. (1984) The Adaptive Effect of Dietary Fish and Safflower Oil on Lipid and Lipoprotein Metabolism in Perfused Rat Liver,Biochim. Biophys. Acta 792, 103–109.
Moir, A.M., and Zammit, V.A. (1994) Effects of Insulin Treatment of Diabetic Rats on Hepatic Partitioning of Fatty Acids Between Oxidation and Esterification, Phospholipid and Acylglycerol Synthesis, and on the Fractional Rate of Secretion of Triacylglycerolin vivo, Biochem. J. 304, 177–182.
Marsh, J.B., Topping, D.L., and Nestel, P.J. (1987) Comparative Effects of Dietary Fish Oil and Carbohydrate on Plasma Lipids and Hepatic Activities of Phosphatidate Phosphohydrolase, Diacylglycerol Acyltransferase and Neutral Lipase Activities in the Rat,Biochim. Biophys. Acta 922, 239–243.
Tijburg, L.B.M., Geelen M.J.H., and van Golde, L.M.G. (1989) Regulation of the Biosynthesis of Triacylglycerol, Phosphatidylcholine and Phosphatidylethanolamine in the Liver,Biochim. Biophys. Acta 1004, 1–19.
Mangroo, D., and Gerber, G.E. (1993) Fatty Acid Uptake inEscherichia coli: Regulation by Recruitment of Fatty Acyl-CoA Synthetase to the Plasma Membrane,Biochem. Cell Biol. 71, 51–56.
Ramsammy, L.S., Haynes, B., Josepovitz, C., and Kaloyanides, G.J. (1993) Mechanism of Decreased Arachidonic Acid in the Renal Cortex of Rats with Diabetes Mellitus,Lipids 28, 433–439.
Ney, D.M., Lasekan, J.B., Spennetta, T. Grahn, M., and Shrago, E. (1989) Effect of Dietary Fat on Individual Long-Chain Fatty Acyl-CoA Eaters in Rat Liver and Skeletal Muscle,Lipids 24, 233–235.
Author information
Authors and Affiliations
About this article
Cite this article
Pai, T., Yeh, YY. Stearic acid unlike shorter-chain saturated fatty acids is poorly utilized for triacylglycerol synthesis and β-oxidation in cultured rat hepatocytes. Lipids 31, 159–164 (1996). https://doi.org/10.1007/BF02522615
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02522615