Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Lipids and cardiovascular/metabolic health

Effects of dietary saturated fat on LDL subclasses and apolipoprotein CIII in men

European Journal of Clinical Nutrition volume 66, pages 1229–1233 (2012)Cite this article

Subjects

Abstract

Background/objectives:

Small dense low-density lipoprotein (LDL) particles and apolipoprotein (apo) CIII are risk factors for cardiovascular disease (CVD) that can be modulated by diet, but there is little information regarding the effects of dietary saturated fat on their plasma levels. We tested the effects of high vs low saturated fat intake in the context of a high beef protein diet on levels and composition of LDL subclasses and on apoCIII levels in plasma and LDL.

Subjects/methods:

Following consumption of a baseline diet (50% carbohydrate (CHO), 13% protein, 38% total fat, 15% saturated fat) for 3 weeks, 14 healthy men were randomly assigned to two reduced CHO high beef protein diets (31% CHO, 31% protein, 38% fat) that differed in saturated fat content (15% vs 8%) for 3 weeks each in a crossover design.

Results:

The high saturated fat (HSF) diet resulted in higher mass concentrations of buoyant LDL I, medium density LDL II and dense LDL III, but not the very dense LDL IV; and significant increases in plasma and LDL apoCIII concentration of 9.4% and 33.5%, respectively. The saturated fat-induced changes in LDL apoCIII were specifically correlated with changes in apoCIII content of LDL IV.

Conclusions:

Taken together with previous observations, these findings suggest that, at least in the context of a lower CHO high beef protein diet, HSF intake may increase CVD risk by metabolic processes that involve apoCIII.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Denke MA . Dietary fats, fatty acids, and their effects on lipoproteins. Curr Atheroscler Rep 2006; 8: 466–471.

    Article  CAS  Google Scholar 

  2. Krauss RM . Lipoprotein subfractions and cardiovascular disease risk. Curr Opin Lipidol 2010; 21: 305–311.

    Article  CAS  Google Scholar 

  3. Mora S, Szklo M, Otvos JD, Greenland P, Psaty BM, Goff DC et al. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2007; 192: 211–217.

    Article  CAS  Google Scholar 

  4. St-Pierre AC, Cantin B, Dagenais GR, Mauriege P, Bernard PM, Despres JP et al. Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Quebec Cardiovascular Study. Arterioscler Thromb Vasc Biol 2005; 25: 553–559.

    Article  CAS  Google Scholar 

  5. Musunuru K, Orho-Melander M, Caulfield MP, Li S, Salameh WA, Reitz RE et al. Ion mobility analysis of lipoprotein subfractions identifies three independent axes of cardiovascular risk. Arterioscler Thromb Vasc Biol 2009; 29: 1975–1980.

    Article  CAS  Google Scholar 

  6. Berneis KK, Krauss RM . Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res 2002; 43: 1363–1379.

    Article  CAS  Google Scholar 

  7. Williams PT, Superko HR, Haskell WL, Alderman EL, Blanche PJ, Holl LG et al. Smallest LDL particles are most strongly related to coronary disease progression in men. Arterioscler Thromb Vasc Biol 2003; 23: 314–321.

    Article  CAS  Google Scholar 

  8. Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV et al. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 2010; 466: 714–719.

    Article  CAS  Google Scholar 

  9. Dreon DM, Fernstrom HA, Campos H, Blanche P, Williams PT, Krauss RM . Change in dietary saturated fat intake is correlated with change in mass of large low-density-lipoprotein particles in men. Am J Clin Nutr 1998; 67: 828–836.

    Article  CAS  Google Scholar 

  10. Krauss RM, Blanche PJ, Rawlings RS, Fernstrom HS, Williams PT . Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr 2006; 83: 1025–1031.

    Article  CAS  Google Scholar 

  11. Mangravite LM, Chiu S, Wojnoonski K, Rawlings RS, Bergeron N, Krauss RM . Changes in atherogenic dyslipidemia induced by carbohydrate restriction in men are dependent on dietary protein source. J Nutr 2011; 141: 2180–2185.

    Article  CAS  Google Scholar 

  12. Clavey V, Lestavel-Delattre S, Copin C, Bard JM, Fruchart JC . Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E. Arterioscler Thromb Vasc Biol 1995; 15: 963–971.

    Article  CAS  Google Scholar 

  13. Wang CS, McConathy WJ, Kloer HU, Alaupovic P . Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C-III. J Clin Invest 1985; 75: 384–390.

    Article  CAS  Google Scholar 

  14. Sacks FM, Alaupovic P, Moye LA, Cole TG, Sussex B, Stampfer MJ et al. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation 2000; 102: 1886–1892.

    Article  CAS  Google Scholar 

  15. Gervaise N, Garrigue MA, Lasfargues G, Lecomte P . Triglycerides, apo C3 and Lp B:C3 and cardiovascular risk in type II diabetes. Diabetologia 2000; 43: 703–708.

    Article  CAS  Google Scholar 

  16. Chivot L, Mainard F, Bigot E, Bard JM, Auget JL, Madec Y et al. Logistic discriminant analysis of lipids and apolipoproteins in a population of coronary bypass patients and the significance of apolipoproteins C-III and E. Atherosclerosis 1990; 82: 205–211.

    Article  CAS  Google Scholar 

  17. Alaupovic P, Mack WJ, Knight-Gibson C, Hodis HN . The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial. Arterioscler Thromb Vasc Biol 1997; 17: 715–722.

    Article  CAS  Google Scholar 

  18. Lee SJ, Campos H, Moye LA, Sacks FM . LDL containing apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients. Arterioscler Thromb Vasc Biol 2003; 23: 853–858.

    Article  CAS  Google Scholar 

  19. Kawakami A, Aikawa M, Libby P, Alcaide P, Luscinskas FW, Sacks FM et al. in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial cells. Circulation 2006; 113: 691–700.

    Article  CAS  Google Scholar 

  20. Kawakami A, Aikawa M, Nitta N, Yoshida M, Libby P, Sacks FM . Apolipoprotein CIIi-induced THP-1 cell adhesion to endothelial cells involves pertussis toxin-sensitive G protein- and protein kinase C alpha-mediated nuclear factor-kappaB activation. Arterioscler Thromb Vasc Biol 2007; 27: 219–225.

    Article  CAS  Google Scholar 

  21. Kawakami A, Aikawa M, Alcaide P, Luscinskas FW, Libby P, Sacks FM et al. induces expression of vascular cell adhesion molecule-1 in vascular endothelial cells and increases adhesion of monocytic cells. Circulation 2006; 114: 681–687.

    Article  CAS  Google Scholar 

  22. Choi SY, Komaromy MC, Chen J, Fong LG, Cooper AD . Acceleration of uptake of LDL but not chylomicrons or chylomicron remnants by cells that secrete apoE and hepatic lipase. J Lipid Res 1994; 35: 848–859.

    CAS  PubMed  Google Scholar 

  23. Pitas RE, Innerarity TL, Mahley RW . Cell surface receptor binding of phospholipid. protein complexes containing different ratios of receptor-active and -inactive E apoprotein. J Biol Chem 1980; 255: 5454–5460.

    CAS  PubMed  Google Scholar 

  24. Warnick GR, Nguyen T, Albers AA . Comparison of improved precipitation methods for quantification of high-density lipoprotein cholesterol. Clin Chem 1985; 31: 217–222.

    CAS  PubMed  Google Scholar 

  25. Friedewald WT, Levy RI, Fredrickson DS . Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

    CAS  Google Scholar 

  26. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  27. Shen MM, Krauss RM, Lindgren FT, Forte TM . Heterogeneity of serum low density lipoproteins in normal human subjects. J Lipid Res 1981; 22: 236–244.

    CAS  PubMed  Google Scholar 

  28. Markwell MA, Haas SM, Bieber LL, Tolbert NE . A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem 1978; 87: 206–210.

    Article  CAS  Google Scholar 

  29. La Belle M, Blanche PJ, Krauss RM . Charge properties of low density lipoprotein subclasses. J Lipid Res 1997; 38: 690–700.

    CAS  PubMed  Google Scholar 

  30. Lee DM, Alaupovic P, Apolipoproteins B . C-III and E in two major subpopulations of low-density lipoproteins. Biochim Biophys Acta 1986; 879: 126–133.

    Article  CAS  Google Scholar 

  31. Davidsson P, Hulthe J, Fagerberg B, Olsson BM, Hallberg C, Dahllof B et al. A proteomic study of the apolipoproteins in LDL subclasses in patients with the metabolic syndrome and type 2 diabetes. J Lipid Res 2005; 46: 1999–2006.

    Article  CAS  Google Scholar 

  32. Mendivil CO, Rimm EB, Furtado J, Chiuve SE, Sacks FM . Low-density lipoproteins containing apolipoprotein C-III and the risk of coronary heart disease. Circulation 2011; 124: 2065–2072.

    Article  CAS  Google Scholar 

  33. Kawakami A, Yoshida M . Apolipoprotein CIII links dyslipidemia with atherosclerosis. J Atheroscler Thromb 2009; 16: 6–11.

    Article  CAS  Google Scholar 

  34. Archer WR, Desroches S, Lamarche B, Deriaz O, Landry N, Fontaine-Bisson B et al. Variations in plasma apolipoprotein C-III levels are strong correlates of the triglyceride response to a high-monounsaturated fatty acid diet and a high-carbohydrate diet. Metabolism 2005; 54: 1390–1397.

    Article  CAS  Google Scholar 

  35. Desroches S, Ruel IL, Deshaies Y, Paradis ME, Archer WR, Couture P et al. Kinetics of plasma apolipoprotein C-III as a determinant of diet-induced changes in plasma triglyceride levels. Eur J Clin Nutr 2008; 62: 10–17.

    Article  CAS  Google Scholar 

  36. Shin MJ, Blanche PJ, Rawlings RS, Fernstrom HS, Krauss RM . Increased plasma concentrations of lipoprotein(a) during a low-fat, high-carbohydrate diet are associated with increased plasma concentrations of apolipoprotein C-III bound to apolipoprotein B-containing lipoproteins. Am J Clin Nutr 2007; 85: 1527–1532.

    Article  CAS  Google Scholar 

  37. Furtado JD, Campos H, Appel LJ, Miller ER, Laranjo N, Carey VJ et al. Effect of protein, unsaturated fat, and carbohydrate intakes on plasma apolipoprotein B and VLDL and LDL containing apolipoprotein C-III: results from the OmniHeart Trial. Am J Clin Nutr 2008; 87: 1623–1630.

    Article  CAS  Google Scholar 

  38. Brousseau ME, Ordovas JM, Osada J, Fasulo J, Robins SJ, Nicolosi RJ et al. Dietary monounsaturated and polyunsaturated fatty acids are comparable in their effects on hepatic apolipoprotein mRNA abundance and liver lipid concentrations when substituted for saturated fatty acids in cynomolgus monkeys. J Nutr 1995; 125: 425–436.

    CAS  PubMed  Google Scholar 

  39. Olin-Lewis K, Krauss RM, La Belle M, Blanche PJ, Barrett PH, Wight TN et al. ApoC-III content of apoB-containing lipoproteins is associated with binding to the vascular proteoglycan biglycan. J Lipid Res 2002; 43: 1969–1977.

    Article  CAS  Google Scholar 

  40. Shin MJ, Krauss RM . Apolipoprotein CIII bound to apoB-containing lipoproteins is associated with small, dense LDL independent of plasma triglyceride levels in healthy men. Atherosclerosis 2010; 211: 337–341.

    Article  CAS  Google Scholar 

  41. Mendivil CO, Zheng C, Furtado J, Lel J, Sacks FM . Metabolism of very-low-density lipoprotein and low-density lipoprotein containing apolipoprotein C-III and not other small apolipoproteins. Arterioscler Thromb Vasc Biol 2010; 30: 239–245.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Beef Checkoff, through the National Cattlemen’s Beef Association and in part by NIH/NCRR UCSF-CTSI grant number UL1 RR024131. We thank the study participants and Robin S Rawlings for subject recruitment and clinical assistance; Casey Geaney, Vanessa Kreger, Joe Orr, Jeff Payumo, Bahareh Sahami and Katie Wojnoonski for laboratory support; and Harriett S Fernstrom and Cewin Chao for assistance in the dietary intervention.

Author information

Authors and Affiliations

  1. Department of Atherosclerosis Research, Children’s Hospital Oakland Research Institute, Oakland, CA, USA

    N Faghihnia, L M Mangravite, S Chiu, N Bergeron & R M Krauss

  2. Sage Bionetworks, Seattle, WA, USA

    L M Mangravite

  3. Touro University California, College of Pharmacy, Vallejo, CA, USA

    N Bergeron

Authors
  1. N Faghihnia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L M Mangravite
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Chiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N Bergeron
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R M Krauss
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R M Krauss.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Faghihnia, N., Mangravite, L., Chiu, S. et al. Effects of dietary saturated fat on LDL subclasses and apolipoprotein CIII in men. Eur J Clin Nutr 66, 1229–1233 (2012). https://doi.org/10.1038/ejcn.2012.118

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2012.118

Keywords

This article is cited by

Search

Advanced search

Quick links