Associations of erythrocyte membrane fatty acids with the concentrations of C-reactive protein, interleukin 1 receptor antagonist and adiponectin in 1373 men.

Dietary and endogenous fatty acids could play a role in low-grade inflammation. In this cross-sectional study the proportions of erythrocyte membrane fatty acids (EMFA) and the concentrations of C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra) and adiponectin were measured and their confounder-adjusted associations examined in 1373 randomly selected Finnish men aged 45-70 years participating in the population based Metsim study in Eastern Finland. The sum of n-6 EMFAs, without linoleic acid (LA), was positively associated with concentrations of CRP and IL-1Ra (r partial=0.139 and r partial=0.115, P<0.001). These associations were especially strong among lean men (waist circumference <94 cm; r partial=0.156 and r partial=0.189, P<0.001). Total n-3 EMFAs correlated inversely with concentrations of CRP (r partial=-0.098, P<0.001). Palmitoleic acid (16:1n-7) correlated positively with CRP (r partial=0.096, P<0.001). Cis-vaccenic acid (18:1n-7) was associated with high concentrations of adiponectin (r partial=0.139, P<0.001). In conclusion, n-6 EMFAs, except for LA, correlated positively with the inflammatory markers. Palmitoleic acid was associated with CRP, whereas, interestingly, its elongation product, cis-vaccenic acid, associated with anti-inflammatory adiponectin.

Combined low-saturated fat intake and high fitness may counterbalance diabetogenic effects of obesity: the DR's EXTRA Study.

We report associations of saturated fat (SF) intake with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), concurrent IFG+IGT and type 2 diabetes (T2DM) at different levels of cardiorespiratory fitness and body mass index (BMI). In a population-based sample (n=1261, age 58-78 years), oral glucose tolerance, 4-day food intake and maximal oxygen uptake were measured. High intake of SF (>11.4 E%) was associated with elevated risk for IFG (4.36; 1.93-9.88), concurrent IFG+IGT (6.03; 1.25-29.20) and T2DM (4.77; 1.93-11.82) in the category of high BMI (>26.5) and high fitness, whereas there was no significantly elevated risk in individuals reporting low intake of SF. Concurrent high BMI and low fitness were associated with elevated risks. In general, SF intake and fitness did not differentiate the risk of abnormal glucose metabolism among subjects with low BMI. Limited intake of SF may protect from diabetogenic effects of adiposity, but only in individuals with high level of fitness.

Association of the FTO gene variant (rs9939609) with cardiovascular disease in men with abnormal glucose metabolism--the Finnish Diabetes Prevention Study.

BACKGROUND AND AIM: The common single nucleotide polymorphism (SNP) in the FTO (fat mass and obesity associated) gene has been consistently associated with an increased risk of obesity. We investigated whether the SNP rs9939609 (T/A) of the FTO is associated with risk factors of cardiovascular diseases (CVD), including serum levels of C - reactive protein (CRP), the chemokine RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted; CCL5), and serum and lipoprotein lipids in the Finnish Diabetes Prevention Study (DPS). Furthermore, we examined whether the rs9939609 increased the CVD risk in the DPS and if these results could be replicated in a larger cross-sectional population-based random sample of Finnish men (the METSIM). METHODS AND RESULTS: In the DPS, altogether 490 (BMI≥25kg/m(2)) subjects with impaired glucose tolerance were genotyped for rs9939609. Cardiovascular morbidity and mortality data were collected during the median follow-up of 10.2 years. The replication study was a population-based cross-sectional study of 6214 men. In the DPS, the AA genotype of rs9939609 was associated, independently of BMI, with increased RANTES (p=0.002) and decreased HDL cholesterol concentrations (p=0.007) in men. During the follow-up, the AA genotype was associated with an adjusted 2.09-fold risk (95% CI 1.17-3.73, p=0.013) of CVD in men. In the METSIM Study, the association with a history of myocardial infarction was replicated in the subgroup of men with type 2 diabetes. CONCLUSION: We suggest that the variation in the FTO gene may contribute to the development of CVD in men with an abnormal glucose metabolism.

Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study.

OBJECTIVE: Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the long-term moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome. DESIGN: Randomized controlled and individualized weight reduction intervention. SUBJECTS: Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 60+/-7 years were randomized either to a weight reduction (WR) (n=28) or a control (n=18) group lasting for 33 weeks. MEASUREMENTS: Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction > or =5%, n=9) and control group (n=10). The results were confirmed using quantitative PCR. RESULTS: In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S (I) and the change in body weight was found (r=-0.44, P=0.026). Downregulation of gene expression (P<0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (-39+/-16%, P<0.0001). Moreover, its expression correlated with insulin sensitivity (r=-0.34, P=0.005) before the intervention and with body adiposity both before (r=0.42, P=0.007) and after (r=0.30, P=0.056) the intervention. CONCLUSION: Genes regulating the extracellular matrix and cell death showed a strong downregulation after long-term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors.

Moderate increase in dietary sucrose does not influence fasting or postprandial serum lipids regardless of the presence of apolipoprotein E2 allele in healthy subjects.

OBJECTIVE: To investigate whether a moderate increase in dietary sucrose intake induces different serum lipid responses in normolipidemic subjects with the epsilon 2 allele compared with subjects without the epsilon 2 allele. DESIGN: Controlled, parallel study. SUBJECTS: There were 15 subjects with the apolipoprotein E (APOE)3/2 genotype and 19 subjects with the APOE 3/3 or 3/4 genotype, whose mean+/-s.d. age was 48+/-14 and 35+/-10 years, respectively. All subjects had normal glucose metabolism. INTERVENTIONS: The subjects were instructed to increase their sucrose intake by 40 g/day for 8 weeks and to decrease the intake of saturated and unsaturated fat to maintain energy balance. Dietary adherence was monitored using food records and the actual increase in sucrose intake was 39.8+/-18.4 g/day. Sixteen subjects (nine with APOE 3/2 genotype, seven with APOE 3/3 or 3/4 genotypes) participated also in an 8 h oral fat tolerance test at the beginning and at the end of the intervention. RESULTS: Body weight remained stable during the intervention. Sucrose intake did not have a significant effect on fasting concentrations of serum total and lipoprotein lipids, plasma glucose, serum insulin, squalene and non-cholesterol sterols in either genotype group. Neither were there any changes in postprandial lipid or insulin responses. CONCLUSIONS: Moderate increase in sucrose intake does not affect fasting or postprandial serum lipid responses in healthy subjects with or without the epsilon 2 allele.

The impact of the leucine 7 to proline 7 polymorphism of the neuropeptide Y gene on postprandial lipemia and on the response of serum total and lipoprotein lipids to a reduced fat diet.

OBJECTIVE: The aim of the study was to examine the impact of the leucine7 to proline7 (Leu7Pro) polymorphism of the NPY gene on postprandial (PP) lipemia, post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities, and the response of serum lipids to a reduced fat diet. DESIGN AND SUBJECTS: Seven middle-aged obese subjects with Leu7Pro genotype were matched with seven subjects with Leu7Leu genotype for gender, age, apolipoprotein E phenotype and BMI. These 14 subjects participated in the oral 8 h fat tolerance test. Sixty-eight slightly obese middle-aged subjects (10 with the Leu7Pro genotype) had participated in intervention studies and consumed a reduced fat diet for 8 weeks. RESULTS: There were no statistically significant differences in PP areas under the curve of plasma total triglycerides (TG), chylomicron TG, VLDL-TG or insulin between the genotype groups. The TG-to-cholesterol (C) ratio in VLDL was significantly lower in the subjects with Leu7Pro genotype compared to those with the Leu7Leu genotype at time points 30 min and 1 h in the fat tolerance test. Heparin-induced activities of LPL or HL or the response of serum total or LDL-C to the reduced fat diet did not differ between the groups. CONCLUSIONS: The NPY genotype neither affects the magnitude of postprandial lipemia induced by a fat tolerance test nor the response of serum total lipids or lipids in different lipoprotein classes to the reduced fat diet. However, this preliminary study suggests that there might be compositional differences in the lipoprotein particles between the genotype groups that affect postprandial lipid metabolism. SPONSORSHIP: The Council for Health Sciences of the Academy of Finland, Kuopio University Hospital and the National Technology Agency, Finland.

Insulin sensitivity after a reduced-fat diet and a monoene-enriched diet in subjects with elevated serum cholesterol and triglyceride concentrations.

BACKGROUND AND AIMS: To investigate the effect of a reduced-fat diet and a monoene-enriched diet (MUFA diet) on serum lipids, glucose and insulin metabolism in subjects with elevated cholesterol and triglyceride concentrations. METHODS AND RESULTS: Eighteen subjects with elevated serum cholesterol and triglyceride concentrations consumed the MUFA diet (39% of energy (E%) as fat and 21 E% monoenes) and the reduced-fat diet (34 E% fat, 16 E% monoenes) for 4 weeks according to a randomized cross-over design. Both periods were preceded by consumption of a standardized baseline diet for 2 weeks. Serum lipid and lipoprotein concentrations were determined at the beginning and end of each diet period. A frequently sampled intravenous glucose tolerance test was performed after the MUFA diet and the reduced-fat diet. Insulin sensitivity index (SI) was 40% higher after the reduced-fat diet than after the MUFA diet (2.42 +/- 0.42 vs 1.73 +/- 0.24 10(-4) min-1 U-1 ml-1, p = 0.018). This change in insulin sensitivity was seen in 13 subjects and was most evident in those who began with the MUFA diet. Compared to the baseline diet (high in saturated fat), both experimental diets lowered serum total and LDL cholesterol concentrations (6.6-6.9%, p < 0.05 and 7.4-8.0%, p < 0.05 respectively). CONCLUSIONS: Both diets were equally effective in lowering serum lipid concentrations, but the reduced-fat diet resulted in better insulin sensitivity.

Relationship of dietary fat to glucose metabolism.

The relationship between dietary fat and glucose metabolism has been recognized for at least 60 years. In experimental animals, high fat diets result in impaired glucose tolerance. This impairment is associated with decreased basal and insulin-stimulated glucose metabolism. Impaired insulin binding and/or glucose transporters has been related to changes in the fatty acid composition of the membrane induced by dietary fat modification. In humans, high-fat diets, independent of fatty acid profile, have been reported to result in decreased insulin sensitivity. Saturated fat, relative to monounsaturated and polyunsaturated fat, appears to be more deleterious with respect to fat-induced insulin insensitivity. Some of the adverse effects induced by fat feeding can be ameliorated with omega-3 fatty acid. Epidemiological data in humans suggest that subjects with higher intakes of fat are more prone to develop disturbances in glucose metabolism, type 2 diabetes or impaired glucose tolerance, than subjects with lower intakes of fat. Inconsistencies in the data may be attributable to clustering of high intakes of dietary fat (especially animal fat) with obesity and inactivity. Metabolic studies suggest that higher-fat diets containing a higher proportion of unsaturated fat result in better measures of glucose metabolism than high-carbohydrate diet. Clearly, the area of dietary fat and glucose metabolism has yet to be fully elucidated.

Dietary cholesterol increases the susceptibility of low density lipoprotein to oxidative modification.

Evidence suggests that oxidative modification of low density lipoprotein (LDL) occurs in vivo, increasing the atherogenecity of the particle. A total of 13 subjects (age range 46-78 years) with an LDL cholesterol concentration >3.36 mmol/l consumed each of four diets for 32-day periods. The diets contained 30% energy as fat of which 2/3 was either corn oil or beef tallow with and without 115 mg/4.2 MJ of supplemental cholesterol in the form of cooked egg yolk. The susceptibility of LDL to oxidation was assessed during a challenge with hemin and hydrogen peroxide, and results are expressed as lag time to oxidation in minutes. Addition of moderate amounts of cholesterol to either the corn oil or beef tallow enriched diet resulted in increased susceptibility of LDL to oxidation (decreased lag time): 69+/-22 min versus 96+/-24 min in the corn oil diet with versus without supplemental cholesterol, respectively, P = 0.006; 82+/-20 min versus 96+/-26 min in the beef tallow diet with versus without supplemental cholesterol, respectively, P = 0.025. A stepwise equation indicated that as plasma oleic acid concentrations increased and/or linoleic acid concentrations decreased, lag time increased (decreased susceptibility to oxidation), whereas as dietary cholesterol concentrations increased, lag time decreased (increased susceptibility to oxidation). In conclusion, these data suggest that addition of a moderate amount of dietary cholesterol to a reduced fat diet rich in polyunsaturated or saturated fatty acids increased the in vitro susceptibility of LDL to oxidation.

A high-trans fatty acid diet and insulin sensitivity in young healthy women.

Epidemiological and experimental studies suggest that a diet rich in saturated fat affects insulin sensitivity. Monoenes and dienes that have an usaturated bond with the trans configuration (trans fatty acids) resemble saturated fatty acids with respect to structure, but no published data are available on the effect of trans fatty acids on insulin sensitivity. Therefore, the effects of diets high in trans fatty acids (TFA diet) and oleic acid (monounsaturated fat [MUFA] diet) on glucose and lipid metabolism were studied in 14 healthy women. Subjects consumed both experimental diets for 4 weeks according to a randomized crossover study design. Both experimental diet periods were preceded by consumption of a standardized baseline diet for 2 weeks. The diets provided 36.6% to 37.9% of energy (E%) as fat. In the TFA diet, there was 5.1 E% trans fatty acids, and in the MUFA diet, 5.2 E% oleic acid, substituted for saturated fatty acids in the baseline diet. A frequently sampled intravenous glucose tolerance test (FSIGT) was performed at the end of the experimental diet periods. Glucose effectiveness (S(G)) and the insulin sensitivity index (S(I)) did not differ after the two experimental diet periods. There was also no difference in the acute insulin response between the diets. The total cholesterol to high-density lipoprotein (HDL) cholesterol ratio and serum total triglyceride, HDL, and low-density lipoprotein (LDL) triglyceride and apolipoprotein B (apoB) concentrations were higher (P < .05) after the TFA diet. In conclusion, in young healthy women, the TFA diet resulted in a higher total/HDL cholesterol ratio and an elevation in triglyceride and apo B concentrations but had no effect on glucose and insulin metabolism compared with the MUFA diet.

Divergent incorporation of dietary trans fatty acids in different serum lipid fractions.

Trans fatty acids may be involved in atherosclerotic vascular diseases. We investigated the incorporation of dietary trans fatty acids and oleic acid into the serum triglycerides (TG), cholesterol esters (CE), and phospholipids (PL). Fourteen healthy female volunteers, aged 23.2+/-3.1 yr (mean+/-SD), body mass index 20.8+/-2.1 kg/m2 participated in this study. All subjects consumed both a trans fatty acid-enriched diet (TRANS diet) and an oleic acid-enriched diet (OLEIC diet) for 4 wk according to a randomized crossover design. Both experimental diet periods were preceded by consumption of a baseline diet for 2 wk which supplied 37% of total energy (E%) as fat: 18 E% from saturated fatty acids (SFA), 12 E% from monounsaturated fatty acids, and 6 E% from polyunsaturated fatty acids. Five E% of the SFA in the baseline diet was replaced by trans fatty acids (18:1t and 18:2c,t + 18:2t,t, where c is cis and t is trans) in the TRANS diet and by oleic acid (18:1n-9) in the OLEIC diet. After the TRANS diet, the proportions of 18:1t and 18:2t increased (P<0.001) in all serum lipid fractions analyzed. The increase of 18:1t in TG and PL (1.80+/-0.28 vs. 5.26+/-1.40; 1.07+/-0.34 vs. 3.39+/-0.76 mol% of total fatty acids, respectively) was markedly higher than that in CE (0.44+/-0.07 vs. 0.92+/-0.26), whereas that of 18:2t was nearly the same in all three fractions. The proportions of palmitic, stearic, arachidonic, and eicosapentaenoic acids in TG, CE, and PL and that of oleic acid in TG and CE were decreased when compared with the baseline value. In contrast, the proportion of palmitoleic acid in TG and PL and that of linoleic acid in PL increased on the TRANS diet. After consumption of the OLEIC diet, the proportion of oleic acid increased in all three lipid fractions analyzed, and the percentage increase was nearly the same in all fractions. In contrast, the proportions of 18:1t in TG and PL and 18:2t in TG and CE decreased when compared with the baseline value. In conclusion, a moderate increase in dietary trans fatty acids resulted in a marked incorporation into serum lipids and decreased the conversion of linoleic acid to its more unsaturated long-chain metabolites. Analysis of 18:1t from serum TG and PL seems to reflect reliably the dietary intake of this fatty acid.

Varying dietary fat type of reduced-fat diets has little effect on the susceptibility of LDL to oxidative modification in moderately hypercholesterolemic subjects.

The effect of the fatty acid composition of reduced-fat diets on the in vitro oxidation of LDL was examined in 14 moderately hypercholesterolemic [low density lipoprotein (LDL) > 3.36 mmol/L] postmenopausal female and male subjects (age 44-78 y). Each subject consumed each of five reduced-fat diets [30 energy percent (E%) fat, 17 E% protein and 53 E% carbohydrate] enriched in beef tallow, canola oil, corn oil, olive oil or rice bran oil (20 E%) for 32-d periods. In vitro oxidation of LDL was assessed by incubating LDL with hemin and hydrogen peroxide, and measuring the time required for the reaction to reach maximum velocity (lag time). LDL lag times were 93.2 +/- 25.8, 95.9 +/- 26.4, 104.2 +/- 32.7, 108.0 +/- 26.6 and 113.1 +/- 24.0 min for corn oil, beef tallow, rice bran oil, canola oil and olive oil periods, respectively. When the data from all dietary phases were pooled, LDL alpha-tocopherol level (r = 0.30, P = 0.01) and plasma 18:1/18:2 ratio (r = 0.22, P = 0.08) were positively related to resistance of LDL to oxidation. Differences induced by the dietary perturbations in LDL content of beta-cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-carotene or beta-carotene, and LDL particle size were not related to resistance of LDL to oxidation. In conclusion, in middle-aged and elderly moderately hypercholesterolemic subjects, the consumption of reduced-fat diets enriched in animal fat or vegetable oils with a relatively wide range of fatty acid profiles did not alter the in vitro susceptibility of LDL to oxidation. The advantages of reducing the saturated fat content of the diet were reflected in lower total and LDL cholesterol levels.

The effect of quality and amount of dietary fat on the susceptibility of low density lipoprotein to oxidation in subjects with impaired glucose tolerance.

OBJECTIVES: We examined the effects of a high fat diet rich in monounsaturated fat (MUFA-diet) and a moderate fat diet rich in polyunsaturated fat (PUFA-diet) on the susceptibility of LDL to oxidation. SUBJECTS: 29 subjects with impaired glucose tolerance. METHODS: After consuming a run-in diet [37% of energy (E%) fat, 18 E% saturated fat] for three weeks, subjects were randomly assigned either to a MUFA-diet (40 E% fat, 19 E% monounsaturated fatty acids) or a PUFA-diet (34 E% fat, 10 E% polyunsaturated fat) for eight weeks. The susceptibility of LDL to oxidation was measured by challenging LDL with hemin and H2O2 and measuring the time for the reaction to reach maximum velocity. Results are expressed as lag time to oxidation in minutes. RESULTS: In the PUFA-diet group (n = 15) lag time tended to decrease during the experimental diet (97 +/- 28 vs 90 +/- 25 min, mean +/- s.d., P = 0.073), whereas in the MUFA-diet group (n = 14) there was no significant change (lag time 96 +/- 24 vs 100 +/- 16 min, P = 0.408). The mean change in lag time was -7 +/- 14 min (-7.2%) in the PUFA-diet group and +4 +/- 16 min (+4.0%) in the MUFA-diet group (P = 0.029, PUFA-diet group vs MUFA-diet group). The alpha-tocopherol concentration in LDL increased significantly (P < 0.01) in both diet groups relative to the run-in diet period, but LDL particle score did not change in either of the diet groups during the dietary intervention. In subjects with impaired glucose tolerance a PUFA-rich diet with a moderate amount of fat tended to increase the susceptibility of LDL to oxidation as compared to a higher fat diet rich in MUFA. Furthermore, the negative mean change in lag time to oxidation found in the PUFA-diet group differed significantly from the slightly positive mean change found in the MUFA-diet group.

A high-stearic acid diet does not impair glucose tolerance and insulin sensitivity in healthy women.

Results in epidemiological and experimental studies suggest that a diet rich in saturated fat may affect insulin sensitivity. However, no published data are available on the effect of stearic acid in this respect. Therefore, we examined the effects of a high-stearic acid diet and a high-oleic acid diet on glucose metabolism, serum lipids and lipoproteins, and blood coagulation factors in 15 healthy female subjects. Subjects followed the two experimental diets for 4 weeks according to a randomized crossover design. Both experimental diet periods were preceded by consumption of a baseline diet for 2 weeks. The diets provided 36% of energy (E%) as fat. In the experimental diets, 5 E% stearic or oleic acid was substituted for 5 E% of saturated fatty acids in the baseline diet. After the experimental diets, no differences were found in the insulin sensitivity index (mean+/-SEM, 5.4+/-1.9 v 5.2+/-1.6 x 10(-4) min(-1) x microU(-1) x mL(-1), nonsignificant [NS]), glucose effectiveness (0.026+/-0.006 v 0.026+/-0.003 min(-1), NS), or first-phase insulin reaction ([FPIR] 368+/-57 v 374+/-66 mU/L x min, NS). The concentration of serum lipids and lipoproteins and blood coagulation factors did not differ after the diet periods. In conclusion, a diet rich in stearic acid did not deteriorate glucose tolerance or insulin action in young healthy female subjects as compared with a diet rich in oleic acid.

Effects of dietary fat modification on fibrinogen, factor VII, and plasminogen activator inhibitor-1 activity in subjects with impaired glucose tolerance.

Our aim was to assess the impact of a monounsaturated fat-enriched (Mono) diet and a diet recommended by the National Cholesterol Education Program (NCEP) on plasma levels of fibrinogen and activities of factor VII (FVII:C) and plasminogen activator inhibitor-1 (PAI-1) and the impact of genetic polymorphisms of these variables (HaeIII, MspI, and 4G/5G polymorphisms, respectively) in 28 subjects with impaired glucose tolerance ([IGT] 17 men and 11 women; mean age, 55.6 +/- 5.5 years). A diet rich in fat and saturated fatty acids served as a baseline diet for 3 weeks. Thereafter, subjects were randomized for the next 8 weeks to either the Mono diet (n = 12) or NCEP diet (n = 18). Fibrinogen levels or PAI-1 activities did not change with either of the diets, but fibrinogen levels were higher (3.4 +/- 0.5 v 4.0 +/- 0.6 g/L, P = .007 at baseline) throughout the study in heterozygous subjects with respect to HaeIII polymorphism. This polymorphism and age accounted for 38% of the variation of fibrinogen levels. MspI polymorphism together with body mass index explained 51% of the variation of FVII:C, which was higher in subjects with the M1M1 genotype compared with M1M2/M2M2 genotypes (127% +/- 21% v 90% +/- 12%, P < .001). FVII:C showed a decrease with the NCEP diet (P < .05), but the decline was confined to M1M1 subjects. PAI-1 activity did not differ significantly between the genotypes. The insulin sensitivity index (SI) obtained by the minimal model method was the main explanatory variable of PAI-1 activity. To conclude, despite good compliance, the fat-modified diet did not alter plasma levels of fibrinogen or PAI-1 in white subjects with IGT. FVII:C levels decreased with the NCEP diet, but this was confined to subjects with the M1M1 genotype.

Different effects of palmitic and stearic acid-enriched diets on serum lipids and lipoproteins and plasma cholesteryl ester transfer protein activity in healthy young women.

The effects of palmitic and stearic acid-enriched diets on serum lipids, lipoproteins, apolipoproteins (apo) A-I and B, and plasma cholesteryl ester transfer protein (CETP) activity were examined in 12 healthy young women. Subjects followed the two experimental diets for 4 weeks according to a randomized crossover design. Both experimental diet periods were preceded by consumption of a baseline diet for 2 weeks. The diets provided 37% of total energy intake (E%) as fat, and differed only with respect to fatty acid composition. There was a substitution of 5E% of palmitic acid or stearic acid in the experimental diets for 5E% of monounsaturated fatty acids in the baseline diet. After the palmitic acid diet, serum total and high-density lipoprotein (HDL) cholesterol and apo A-I concentrations were higher (8%, P = .015, 9%, P = .040, and 11%,P = .011, respectively) and mean serum low-density lipoprotein (LDL) cholesterol concentration tended to be higher (8%, P = .077) as compared with values after the stearic acid diet. Plasma CETP activity increased in the palmitic acid diet as compared with the stearic acid diet (12%, P = .006). In conclusion, palmitic acid and stearic acid-enriched diets had different effects on serum lipids and lipoproteins and also on plasma CETP activity in young healthy women.

Impact of hydrogenated fat consumption on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein to oxidation in moderately hypercholesterolemic individuals.

The effects of replacing corn oil with corn oil margarine in stick form on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein (LDL) to oxidation were assessed in 14 middle-aged and elderly men and women aged 63 +/- 12 years (mean +/- SD) with moderate hypercholesterolemia (mean LDL-cholesterol [LDL-C], 4.24 +/- 0.59 mmol/L at the time of recruitment). Subjects consumed each of two diets for 32-day periods, one enriched in corn oil, which contained 30% of energy as fat (7% saturated fatty acid [SFA], 9% monounsaturated fatty acid [MUFA] [0.4% 18:1n9 trans], and 11% polyunsaturated fatty acid [PUFA]) and 85 mg cholesterol/4.2 MJ, and one enriched in stick corn oil margarine, which contained 30% fat (8% SFA, 12% MUFA [4.2% 18:1n9trans], and 8% PUFA) and 77 mg cholesterol/4.2 MJ. Both diets were isocaloric and supplied by a metabolic research kitchen. Mean total cholesterol levels were lowest (P = .039) when subjects consumed the corn oil-enriched diet (5.01 +/- 0.51 mmol/L) as compared with the margarine-enriched diet (5.30 +/- 0.58 mmol/L). LDL-C levels were 3.24 +/- 0.51 and 3.50 +/- 0.54 mmol/L when subjects consumed corn oil-and margarine-enriched diets, respectively (P = .058). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) or triglyceride concentrations between the two experimental periods. Consumption of the margarine-enriched diet versus the corn oil-enriched diet tended to result in lower cholesterol fractional synthetic rates ([C-FSRs] 0.0466 +/- 0.0175 and 0.0668 +/- 0.0298, respectively, P = .080) and cholesterol absolute synthetic rates ([C-ASRs] 1.1761 +/- 0.5375 and 1.6954 +/- 0.8685, respectively, P = .092); however, differences did not reach statistical significance. Consumption of the margarine-enriched diet versus the corn oil-enriched diet resulted in a significantly higher concentration of alpha-tocopherol in both plasma and LDL(P = .004 and P = .011, respectively). LDL particle size tended to be smaller after subjects consumed the margarine-enriched diet versus the corn oil-enriched diet (P = .103). Susceptibility of LDL to oxidation was similar after consumption of the corn oil- and margarine-enriched diets. These data suggest that an increased rate of endogenous cholesterol synthesis did not contribute to the higher plasma cholesterol concentrations during the period when subjects consumed the margarine-enriched diet. Therefore, the increase in cholesterol concentration resulting from margarine consumption was likely attributable, at least in part, to a decreased catabolic rate of cholesterol. Additionally, susceptibility of LDL to in vitro oxidation was not altered by consumption of hydrogenated fat.

Lauric and palmitic acid-enriched diets have minimal impact on serum lipid and lipoprotein concentrations and glucose metabolism in healthy young women.

Fifteen healthy young women were fed diets enriched to 4% of energy with either palmitic acid (as palm oil) or lauric acid (as coconut oil). A randomized crossover study design was used so that subjects followed the two experimental diets for 4 wk, both preceded by consumption of a baseline diet for 2 wk. The experimental diets differed only with respect to the fatty acid composition: there was a substitution of 4% of energy intake with palmitic acid or lauric acid in the experimental diets for 4% of energy as monoenes in the baseline diet. There were no differences in the concentration of serum total or lipoprotein lipids, apolipoproteins A-I and B, and lipoprotein (a) or plasma cholesteryl ester transfer protein activity between the experimental diet periods. The VLDL cholesterol concentration (0.38 +/- 0.05 vs. 0.51 +/- 0.05 mmol/L, means +/- SEM, P = 0.01] and plasma cholesteryl ester transfer protein activity [78 +/- 5 vs. 88 +/- 6 mumol/(h.L), P = 0.007) were greater at the end of the lauric acid diet period than at the end of the preceding baseline diet period. No differences were found in glucose effectiveness, insulin sensitivity index or insulin secretion measured by the intravenous glucose tolerance test (Minimal Model method). In conclusion, in terms of serum lipids, lipoproteins, and glucose metabolism, palmitic acid was equal to lauric acid at 4% of total energy intake exchange, and both of these saturated fatty acids were comparable to a 4% of total energy intake exchange with monoenes in healthy young women.