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.
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.
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.
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.
It is well established that increased saturated fat intake raises low-density lipoprotein (LDL) cholesterol.1 However, LDL is comprised of a spectrum of distinct particle subclasses differing in metabolic properties and atherogenic potential,2 and effects of saturated fat on these subclasses have been less extensively evaluated. Lipoprotein profiles characterized by smaller, denser LDL particles are associated with higher cardiovascular disease (CVD) risk than those with predominately larger LDL.2, 3, 4, 5 Small dense LDL have a number of properties that may contribute to atherosclerosis risk, including lower affinity for LDL receptors, greater binding to arterial proteoglycans and higher oxidative susceptibility than more buoyant LDL.6 It has been reported that very small LDL are particularly strongly associated with coronary atherosclerosis progression,7 a property consistent with the recent finding that a single-nucleotide polymorphism strongly associated with plasma LDL cholesterol and risk of myocardial infarction is specifically related to plasma levels of very small LDL.8
Intake of saturated fat, particularly myristic (14:0) and palmitic (16:0) acids, but not stearic acid (18:0), has been found to correlate with levels of large LDL I.9 Moreover, in the setting of a low carbohydrate (CHO) mixed protein diet, the higher levels of LDL that resulted from increased saturated fat intake were found to be entirely due to increases in larger LDL particles.10 Yet we recently found that consumption of increased saturated fat in conjunction with a high beef protein, low CHO diet resulted in an increase in LDL particles across the full-size spectrum, raising the possibility that the effects of saturated fat on LDL particles may depend on dietary context.11 We here describe analyses of lipid and protein composition of LDL subfractions isolated from a subset of participants in that study, with the aim of determining whether higher intake of saturated fat resulted in compositional changes in specific LDL particles. We also examined the effects of higher vs lower saturated fat on LDL content of apolipoprotein (apo) CIII, an important regulator of lipoprotein metabolism by virtue of its capacity to inhibit lipoprotein lipase activity and reduce receptor-mediated clearance of apoB-containing particles.12, 13 The association of apoCIII with apoB-containing lipoproteins has repeatedly been linked with increased CVD risk,14, 15, 16, 17, 18 an effect that may be related to the metabolic effects and/or its pro-inflammatory properties of apoCIII.19, 20, 21 Finally, we tested for diet-induced changes in LDL content of apoE, a determinant of receptor-mediated plasma lipoprotein clearance.22, 23
Subjects and methods
Study design and diets
These analyses were performed in a subgroup of 14 healthy male participants in a controlled, randomized, crossover dietary intervention trial aimed at evaluating plasma lipid and lipoprotein responses to high vs low saturated fat intake in the context of replacement of CHO with protein derived to a large extent from beef.11 All participants consumed a baseline diet for 3 weeks, after which they were assigned in random order to a low CHO high beef protein diet that was either high (15%) or low (8%) in saturated fat for 3 weeks. Each 3-week experimental diet period was separated by a 2-week washout during which participants resumed consumption of their habitual diet. The experimental diets were designed to be low in CHO and high in beef protein, and to differ in saturated fat content (Table 1).
Diets were prepared in the metabolic kitchen of the University of California, San Francisco (UCSF) Clinical and Translational Studies Institute (CTSI). After preparation, entrees were frozen and delivered to participants on a weekly basis. Participants were provided with lunch and dinner meals and were asked to prepare their own breakfasts and snacks, according to menus developed in accordance with their assigned diet. Participants were weighed weekly and energy intake was adjusted if weight deviated by more than ±3%. Dietary adherence was promoted through regular telephone contacts and weekly meetings with the dietitians. The nutrient composition of the diets was assessed using the Nutrition Data System for Research 2007MN Food and Nutrient Database (Nutrition Coordinating Center, University of Minnesota, Minneapolis, MN, USA) and confirmed by compositional analysis of daily menus (Covance Inc., Kalamazoo, MI, USA). Daily use of a pedometer allowed monitoring of participants’ physical activity, which was required to remain stable for the duration of the study.
Participants were recruited from our extensive recruitment database and the community primarily through internet advertisements. They were healthy, non-smoking men ⩾18 years of age, free of chronic disease in the past 5 years, and not taking medications known to affect lipid metabolism. Other eligibility criteria included a body mass index between 20–35 kg/m2, total cholesterol (TC) and LDL cholesterol less than the 95th percentile for their age and gender, triglyceride <500 mg/dl, fasting blood glucose <126 mg/dl, resting blood pressure <150/90 mm Hg and hematocrit ⩾36%. Participants were asked to refrain from alcohol and dietary supplements for the duration of the study. All participants gave informed consent under a protocol approved by the Institutional Review Board of Children’s Hospital and Research Center Oakland. The study is registered at clinicaltrials.gov (NCT00852267). One participant was eliminated from the present analysis due to a triglyceride level >2 s.d. above the mean for all diets (baseline: 270 mg/dl, low saturated fat (LSF): 171 mg/dl and high saturated fat (HSF): 451 mg/dl), as this may affect apoCIII metabolism.
Fasting plasma samples were prepared from venous blood collected in tubes containing Na2EDTA (1.4 g/l) and a preservative cocktail of protease and bacterial inhibitors. Blood and plasma were kept at 4 °C throughout processing. Plasma TC and triglyceride concentrations were determined by enzymatic procedures on an Express 550 Plus analyzer (Ciba Corning, Oberlin, OH, USA). HDL cholesterol was measured after dextran sulfate precipitation of plasma,24 and LDL cholesterol was calculated from the formula of Friedewald et al.25 Measurements were regularly monitored by the standardization program of the Centers for Disease Control-National Heart, Lung and Blood Institute. Plasma apoB concentrations were measured by an immunoturbidometric assay (Bacton Assay Systems, San Marcos, CA, USA and Express 550 Plus analyzer, Ciba Corning). ApoE and apoCIII were measured in triplicate by sandwich-style enzyme-linked immunosorbent assay with commercially available goat anti-human apoE and apoCIII, respectively (International Immunology Corp., Murrieta, CA, USA). HDL apoCIII was measured in the supernatant obtained after dextran sulfate precipitation24 of apoB-containing lipoproteins. The concentration of apoCIII in apoB-containing lipoproteins (non-HDL apoCIII) was calculated by difference (plasma − HDL apoCIII concentration). Glucose concentrations were measured enzymatically (Express 550 Plus Analyzer, Ciba Corning). Insulin concentrations were measured with enzyme-linked immunosorbent assay (Millipore, Billerica, MA, USA). The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated from glucose and insulin concentrations:26 HOMA-IR=(insulin (μU/ml) × glucose (mmol/l))/22.5.
Isolation of LDL and LDL subfractions
LDL were isolated from the serum of each participant by ultracentrifugation under standard conditions.27 The LDL fractions were grouped into four major LDL subclasses, based on density, designated LDL I (density <1.028), LDL II (1.028–1.034), LDL III (1.034–1.044) and LDL IV (1.044–1.060).6
Chemical composition of LDL subfractions
Fractions were analyzed for concentrations of TC (Siemens Medical Solutions Diagnostics, Tarrytown, NY, USA), triglyceride (Sigma-Aldrich, St. Louis, MO, USA), free cholesterol (FC) (Wako Chemicals USA, Inc., Richmond, VA, USA) and phospholipids (Wako Chemicals USA, Inc., Richmond, VA, USA) using commercially available enzymatic kits. Cholesterol ester (CE) concentrations were calculated as [(TC − FC) × 1.68]. Protein concentrations were determined by a modification of the method of Lowry et al.28 using bovine serum albumin as the standard. The lipoproteins were read on an EL × 808 Ultra Microplate Reader (Bio-Tek Instruments, Inc., Winooski, VT, USA). Assays were carried out in duplicate with standards, controls and unknowns on the same 96-well plate, and with coefficients of variation within 10%. On an average over 90% of the plasma apolipoproteins (B, CIII and E) in LDL subclasses were recovered from density gradient ultracentrifugation.
JMP statistical software (version 7.0; SAS Institute, Cary, NC, USA) was used for statistical analysis. Data are presented as means±s.d. Shapiro–Wilk test was used to test the skewness of the distributions. Non-normally distributed variables were log-transformed before analysis. Paired t-tests were used to evaluate differences in lipids, lipoproteins and apolipoproteins between the diets and across LDL subclasses. Spearman’s correlation coefficients were used to evaluate the relationship between diet-induced changes in lipids, lipoproteins and apolipoproteins. P-values <0.05 were considered statistically significant.
Participant characteristics at baseline
The mean (±s.d.) age of the men was 44.5±14.4 years (range: 24–67 years), weight was 78.6±10.8 kg, body mass index was 25.0±2.4 kg/m2 and body fat was 20.9±6.3%. The participants had normal fasting blood glucose (89.3±8.0 mg/dl), plasma insulin concentrations (5.1±2.4 μU/ml) and HOMA-IR (1.1±0.6).
Plasma lipid and lipoprotein response to dietary intervention
In the context of moderate CHO intake, consumption of LSF vs HSF intake resulted in an overall more favorable lipid profile with lower plasma TC (P=0.007), LDL cholesterol (P=0.007), TC/HDL cholesterol (P=0.0004), apoB (P=0.06) and apoCIII concentrations (P=0.03) (Table 2).
Compositional characteristics of LDL and LDL subclasses at baseline
Analyses of lipid and apolipoprotein content were performed on total LDL and LDL subfractions (Table 3). The baseline compositional trends of LDL subclasses for percent FC, cholesterol esters, phospholipids and protein across LDL subclasses were consistent with previous findings.6, 27, 29 Percent triglyceride at baseline was greater in LDL I vs LDL II-IV.
LDL I and LDL IV particles were significantly lower in number (as measured by apoB) and total mass concentration compared with LDL II and III, with LDL III being the most abundant subfraction (Table 3). ApoCIII and apoE levels were highest in LDL IV (Table 3). We also calculated the relative enrichment of apoCIII and apoE per apoB molecule of total LDL and across LDL subclasses (Table 4). ApoCIII/apoB and apoE/apoB ratios were significantly higher in LDL I and IV than in LDL II and III with no significant difference between LDL I and IV.
Effects of dietary saturated fat on compositional characteristics of LDL and LDL subclasses
In the setting of moderate CHO intake, HSF vs LSF intake significantly increased LDL total mass concentration by 15.2% and LDL apoCIII content by 33.5% (Table 5). The change in LDL mass was attributable to significant increases in the mass concentrations of LDL subclasses I, II and III by 19.0%, 20.1% and 16.5%, respectively, but was significantly correlated only with changes in LDL III (r=0.65, P=0.01) (data not shown). The relative enrichment of apoCIII per apoB in total LDL tended to increase with HSF vs LSF intake (P=0.07) (data not shown). Saturated fat-induced increases in plasma and LDL apoCIII were positively and significantly correlated with changes in LDL IV apoCIII (Table 6 and Figure 1), but not LDL I-III apoCIII. No significant changes in apoE content were observed in total LDL or LDL subclasses with HSF vs LSF intake (Table 5).
Our results show that in the context of a reduced CHO, high beef protein diet, the increase in plasma and LDL cholesterol with high vs low saturated fat is associated with concurrent increases in the concentration of plasma and LDL apoCIII and the mass of large, medium and small LDL particles. The change in total LDL apoCIII was correlated with changes in apoCIII in the LDL IV fraction (ρ=0.66). Consistent with previous reports, the concentration of apoCIII was significantly higher in LDL IV compared with other LDL subfractions (Table 3).30, 31 Increased LDL apoCIII has been shown to be an important marker of CVD risk that is independent of standard lipid risk factors and in fact much of the risk ordinarily attributed to LDL appears to be due to LDL particles that contain apoCIII.18, 32 The increased apoCIII content of small dense LDL and greater affinity of these particles for arterial proteoglycans31 may increase interaction with the arterial wall and facilitate oxidative modification. Furthermore, clinical observations suggest that apoCIII may has a direct role in the development of atherosclerosis by activating inflammatory responses through monocyte–endothelial interactions.33
Consistent with the results of the larger study, we found that saturated fat increased the mass of LDL I-III with no change in LDL IV (Table 5). This contrasts with results from an earlier study, where high (15%) vs low (9%) saturated fat intake in the context of a diet high in protein from mixed sources increased LDL cholesterol primarily through elevations in mass of larger LDL without changes in levels of small LDL particles.10 Although the basis for the differing findings is unclear, one explanation may be related to differences in dietary protein source between the two studies.
To our knowledge, this study is the first to show significant increases in plasma and LDL apoCIII with saturated vs monounsaturated fat feeding, with all other macronutrients held constant. Others34, 35, 36, 37 have reported diet-induced increases in plasma apoCIII and concurrent elevations in plasma triglycerides, mainly as a result of increased dietary CHO intake. In contrast to the current study, the saturated fat-mediated changes in plasma and LDL apoCIII were independent of changes in triglycerides. Studies in cynomolgus monkeys have shown significantly higher hepatic apoCIII mRNA levels with saturated vs monounsaturated fat intake.38 Consistent with our observations, the increase in hepatic apoCIII in the monkey studies was not paralleled by an increase in plasma triglycerides. Thus, the saturated fat-induced rise in plasma and LDL apoCIII in our study may be due to the increase in production of apoCIII at the transcriptional level.
ApoCIII enriched apoB-containing lipoproteins may be particularly atherogenic by virtue of their decreased affinity for the LDL receptor12 and increased binding to extracellular vascular proteoglycans.39 LDL with apoCIII strongly predicts coronary events in diabetic patients independent of other lipids.18 Notably, in plasma isolated from patients with metabolic syndrome or type 2 diabetes mellitus, the content of apoCIII in small dense LDL has been shown to be significantly correlated with an enhanced affinity of these particles for arterial proteoglycans.31 A recent report in 141 healthy middle-aged men showed a significant positive association between plasma apoCIII concentration and levels of the smallest of LDL subclasses (LDL IV) independent of plasma triglycerides and concluded that enrichment of apoCIII in small dense LDL may contribute to the metabolic and pathologic properties of these particles.40 A recent kinetic study41 showed accelerated hepatic lipase-mediated conversion of light LDL to dense LDL, when precursor particles were enriched with apoCIII. It is possible that in vivo, apoCIII positively modulates hepatic lipase to increase dense LDL particle concentrations. On the basis of the results from the total set of individuals participating in the current dietary intervention (n=40),11 higher saturated fat intake combined with high beef intake tended to increase the activity of hepatic lipase activity (P=0.08), supporting the role of hepatic lipase in promoting the formation of small dense LDL.
Limitations of the current study include a small sample size, providing limited power for multivariable statistical adjustments and the potential for type I error as a result of multiple testing. Nonetheless, the present findings suggest that increased levels of small, apoCIII-containing LDL may contribute to the adverse effects of a diet high in beef and saturated fat on CVD risk.
Denke MA . Dietary fats, fatty acids, and their effects on lipoproteins. Curr Atheroscler Rep 2006; 8: 466–471.
Krauss RM . Lipoprotein subfractions and cardiovascular disease risk. Curr Opin Lipidol 2010; 21: 305–311.
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.
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.
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.
Berneis KK, Krauss RM . Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res 2002; 43: 1363–1379.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Warnick GR, Nguyen T, Albers AA . Comparison of improved precipitation methods for quantification of high-density lipoprotein cholesterol. Clin Chem 1985; 31: 217–222.
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.
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.
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.
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.
La Belle M, Blanche PJ, Krauss RM . Charge properties of low density lipoprotein subclasses. J Lipid Res 1997; 38: 690–700.
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.
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.
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.
Kawakami A, Yoshida M . Apolipoprotein CIII links dyslipidemia with atherosclerosis. J Atheroscler Thromb 2009; 16: 6–11.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The authors declare no conflict of interest.
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) doi:10.1038/ejcn.2012.118
- saturated fat
- low-density lipoprotein
- apolipoprotein CIII
- cardiovascular disease
- LDL subfractions
Effects of carbohydrate-restricted diets on low-density lipoprotein cholesterol levels in overweight and obese adults: a systematic review and meta-analysis
Nutrition Reviews (2019)
Canadian Journal of Physiology and Pharmacology (2019)
Current Atherosclerosis Reports (2019)
A 5-day high-fat diet rich in cottonseed oil improves cholesterol profiles and triglycerides compared to olive oil in healthy men
Nutrition Research (2018)
Prostaglandins, Leukotrienes and Essential Fatty Acids (2018)