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Journal of Lipid Research, Vol. 43, 2155-2163, December 2002
Copyright © 2002 by Lipid Research, Inc.

Myristic acid increases dense lipoprotein secretion by inhibiting apoB degradation and triglyceride recruitment

Emma Kummrow^*, M. Mahmood Hussain^*,, Meihui Pan, Julian B. Marsh^*,** and Edward A. Fisher^1,*,

^* Department of Biochemistry, Medical College of Pennsylvania-Hahnemann School of Medicine, Philadelphia, PA 19129
Department of Anatomy and Cell Biology, SUNY Health Science Center, Brooklyn, NY 11203
Department of Medicine and The Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029
^** Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111

¹ To whom correspondence should be addressed. e-mail: edward.fisher{at}mssm.edu

Fatty acids of varying lengths and saturation differentially affect plasma apolipoprotein B-100 (apoB-100) levels. To identify mechanisms at the level of production, rat hepatoma cells, McA-RH7777, were incubated with [³⁵S]methionine and either fatty acid-BSA complexes or BSA alone. There were increases in labeled apoB-100 secretion with saturated fatty acids palmitic and myristic (MA) (153 ± 20% and 165 ± 11%, respectively, relative to BSA). Incubation with polyunsaturated docosahexaenoic acid (DHA) decreased secretion to 26 ± 2.0%, while monounsaturated oleic acid (OA) did not change it. In pulse-chase studies, MA treatment resulted in reduced apoB-100 degradation, in agreement with its promotion of secretion. In triglyceride (TG) studies, synthesis was stimulated equally by OA, MA, and DHA, but TG secretion was relatively decreased with MA and DHA. With OA, the majority of newly secreted apoB100-lipoproteins was d 1.006, but with MA, they were much denser (1.063 < d). Furthermore, the relative recruitment of newly synthesized TG to lipoproteins was impaired with MA.

We conclude that mechanisms for effects of specific dietary fatty acids on plasma lipoprotein levels may include changes in hepatic production. In turn, hepatic production may be regulated by specific fatty acids at the steps of apoB-100 degradation and the recruitment of nascent TG to lipoprotein particles.

Abbreviations: DHA, docosahexaenoic acid; MA, myristic acid; OA, oleic acid; PA, palmitic acid; SFA, saturated fatty acid(s); TG, triglyceride(s)

Supplementary key words saturated fatty acid • palmitic acid • oleic acid • polyunsaturated fatty acid • n-3 fatty acid • DHA • VLDL

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