SFA Diet Research Articles

The cholesterolaemic effects of dietary fats in cholesteryl ester transfer protein transgenic mice.

In order to investigate the role of cholesteryl ester transfer protein (CETP) in the cholesterolaemic response to dietary fats, we analysed plasma lipid profiles of CETP-transgenic and control C57BL/6 mice fed standard chow (AIN-93G; AIN), a low-fat diet, and diets high in butter (saturated fatty acids; SFA), high-oleic acid safflower oil (monounsaturated fatty acids; MUFA), and safflower oil (polyunsaturated fatty acids; PUFA) for 5 weeks. Each group contained four or five mice. There were significant diet and dietxgenotype effects on plasma total cholesterol (TC; and respectively), liver TC ( and respectively), and esterified cholesterol (EC; and respectively); diet effects on plasma triacylglycerol liver free cholesterol and body weight a genotype effect on body-weight gain and a dietxgenotype effect on energy intake In transgenic mice the SFA diet caused significantly higher plasma TC than the PUFA diet In control mice MUFA and PUFA diets, but not the SFA diet, caused significantly higher plasma TC than the low-fat and AIN diets Transgenic mice fed PUFA had lower plasma TC while transgenic mice fed MUFA had lower LDL+VLDL-cholesterol than controls in the same dietary groups. Transgenic mice fed MUFA and PUFA diets also had significantly higher liver TC and respectively) and EC and respectively) than controls fed the same diets. In the present study we showed that: (1) CETP transgenic mice had a cholesterolaemic response to dietary fats similar to that in human subjects; (2) CETP transgenic mice fed PUFA showed significantly lower plasma TC, while those fed MUFA had lower LDL+VLDL-cholesterol than controls; (3) hepatic accumulation of cholesterol, possibly resulting from the combination of the enhanced cholesteryl ester transfer to apolipoprotein B-containing lipoproteins and increased hepatic uptake of cholesterol, may contribute to the cholesterol-lowering effect of MUFA and PUFA in CETP-transgenic mice; (4) CETP may play a role in appetite and/or energy regulation.

Low-fat and high–monounsaturated fatty acid diets decrease plasma cholesterol ester transfer protein concentrations in young, healthy, normolipemic men

Cholesterol ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to apolipoprotein (apo) B-containing lipoproteins. The possible atherogenic role of this protein is controversial. Diet may influence plasma CETP concentrations. The objective was to determine whether the changes in plasma lipids observed after consumption of 2 lipid-lowering diets are associated with changes in plasma CETP concentrations. : We studied 41 healthy, normolipidemic men over 3 consecutive 4-wk dietary periods: a saturated fatty acid-rich diet (SFA diet: 38% fat, 20% saturated fat), a National Cholesterol Education Program Step I diet (NCEP Step I diet: 28% fat, 10% saturated fat), and a monounsaturated fatty acid-rich diet (MUFA diet: 38% fat, 22% monounsaturated fat). Cholesterol content (27.5 mg/MJ) was kept constant during the 3 periods. Plasma concentrations of total, LDL, and HDL cholesterol; triacylglycerol; apo A-I and B; and CETP were measured at the end of each dietary period. Compared with the SFA diet, both lipid-lowering diets significantly decreased plasma total and LDL cholesterol, apo B, and CETP. Only the NCEP Step I diet lowered plasma HDL cholesterol. Positive, significant correlations were found between plasma CETP and total (r = 0.3868, P < 0.0001) and LDL (r = 0.4454, P < 0.0001) cholesterol and also between changes in CETP concentrations and those of total (r = 0.4543, P < 0.0001) and LDL (r = 0.4554, P < 0.0001) cholesterol. The isoenergetic substitution of a high-saturated fatty acid diet with an NCEP Step I or a high-monounsaturated fatty acid diet decreases plasma CETP concentrations.

Acute ingestion of different dietary fatty acid species modulates postprandial lipid responses in New Zealand white rabbits

Although several investigations have linked the degree of fatty acid saturation to plasma lipid responses in the postprandial state, further evaluation is necessary. In this study, we compared the effect of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids on postprandial lipid metabolism using complementary in vivo and in vitro approaches. Fat (10 g) cholesterol (0.5 g) test meals that provided either lard (SFA), olive oil (MUFA), or sunflower oil (PUFA) were ingested by chow-fed New Zealand white rabbits ( n = 8). In addition, hepatic uptake of triglyceride-cholesterol-rich lipoproteins (TCRL) isolated from rabbits chronically ingesting SFA, MUFA, or PUFA diets was measured using freshly isolated chow-fed rabbit hepatocytes. Whatever dietary fatty acids ingested, postprandial triglyceridemia and occurrence of radiolabelled dietary lipids in plasma were not markedly different. Conversely, SFA induced higher postprandial cholesterolemia and phospholipemia than MUFA ( P < 0.05) whereas PUFA prevented postprandial cholesterol increase. TCRL disappearance from cultured liver cell media was delayed with SFA-rich TCRL and faster with PUFA whereas MUFA-rich TCRL showed an intermediate figure. From these data, we conclude that SFA, MUFA, and PUFA elicited different postprandial plasma and lipoprotein lipid responses. The fatty acid composition of TCRL had a major impact on their subsequent metabolism, especially uptake by cultured hepatocytes. The SFA-induced hypercholesterolemia could be related to an altered hepatic uptake whereas a faster clearance and hepatic uptake could explain the cholesterol-lowering effect of PUFA in rabbits. MUFA, like PUFA, accelerate uptake by hepatocytes but favor cholesterol ester enrichment of TCRL.

Regulation of apolipoprotein B—containing lipoproteins by vitamin C level and dietary fat saturation in guinea pigs

Effects of suboptimal and adequate vitamin C, with varying dietary fat saturation, on hepatic cholesterol and plasma lipoprotein concentrations and metabolism were studied in guinea pigs fed 15% ( wt wt ) fat/0.04% cholesterol diets. Fat mixtures were either 49% saturated (SFA) (24% lauric acid) or 53% polyunsaturated fatty acid (PUFA) linoleic acid with vitamin C at 50 (suboptimal) or 500 (adequate) mg/kg diet. Guinea pigs fed suboptimal vitamin C had 15% lower hepatic active 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and 25% lower low-density lipoprotein (LDL; apolipoprotein [apo] B/E) receptor number, 20% higher acyl-CoA:cholesterol acyltransferase (ACAT) activity, 28% higher triacylglycerol (TAG) and cholesteryl ester concentrations, and increased very—low-density lipopoprotein (VLDL) apo B secretion rates in comparison to animals fed adequate vitamin C. Intake of suboptimal vitamin C lowered plasma high-density lipoprotein (HDL) cholesterol concentrations by 45% and increased plasma TAG, total and VLDL/LDL cholesterol, and cholesteryl ester transfer protein (CETP) activity by 40%, 50%, and 30%, respectively. The hyperlipidemic effects of suboptimal vitamin C were more pronounced with intake of the SFA diet. These data demonstrate that low vitamin C intake results in a pattern of changes in whole-body cholesterol and lipoprotein metabolism that are related to increased risk of cardiovascular disease (CVD).

Saturated fat and simple carbohydrates elevate plasma LDL cholesterol concentrations by specific alterations on hepatic cholesterol metabolism

We investigated the independent and interactive effects of saturated fat and simple carbohydrates on plasma and hepatic cholesterol in guinea pigs fed semipurified diets containing 19% fat ( w w ) either high in lauric + myristic (SFA), oleic (MUFA), or linoleic (PUFA) and 33.5% ( w w ) of carbohydrates either sucrose or starch for four weeks. Plasma LDL cholesterol concentrations were 40% higher in the simple carbohydrate groups compared with starch-fed animals (P <0.005). SFA-fed guinea pigs had 75% higher plasma LDL cholesterol than did those fed MUFA or PUFA diets (P< 0.0001). In addition, SFA significantly decreased HDL cholesterol levels by 100–130% compared to MUFA or PUFA diets which had similar effects. Sucrose intake resulted in increased plasma apoB concentrations compared with starch intake (P = 0.001). SFA intake also increased plasma apoB levels by 50% compared with MUFA or PUFA diets (P<0.00001). Guinea pigs fed SFA diets had 60% lower hepatic LDL receptor number than those fed MUFA and PUFA diets while sucrose intake reduced the number of hepatic LDL receptors by 30% (P < 0.01). Hepatic ACAT activity was 1.7 fold higher in animals fed sucrose diets compared with those fed starch (P<0.0001). These studies suggest that SFA and sucrose independently raise plasma LDL cholesterol levels by distinct mechanisms that alter hepatic cholesterol homeostasis and affect the synthesis and catabolism of lipoproteins.

Effects of the ratio of polyunsaturated and monounsaturated fatty acid to saturated fatty acid on rat plasma and liver lipid concentrations

The effects of dietary monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid + MUFA/saturated fatty acid (PUFA + MUFA/SFA) ratio on plasma and liver lipid concentrations were studied. In experiment I, when rats were fed with 40% fat (energy%, PUFA/SFA ratio 1.0) and 1% (w/w) cholesterol (C) diets for 21 d, a large amount of MUFA (28.1 energy%, PUFA + MUFA/SFA = 5.7) in the diet was found to increase the plasma total C, triacylglycerol (TAG), and phospholipid (PL) as compared with the low-MUFA diet (7.0 energy%, PUFA + MUFA/SFA = 1.4). The plasma very low density lipoprotein (VLDL)-C, VLDL-TAG, VLDL-PL, and low density lipoprotein (LDL)-C increased significantly in the high-MUFA diet group, but high density lipoprotein (HDL)-C did not change significantly. The high-MUFA diet resulted in greater accumulation of liver C but lesser accumulation of TAG. In experiment II, when dietary SFA was fixed at a certain level (13.2 energy%; PUFA + MUFA/SFA = 2.0), rats given a larger amount of MUFA (23.1 energy%; PUFA/MUFA = 0.2; MUFA/SFA = 1.8) showed higher plasma and liver C levels than did the low-MUFA diet (7.7 energy%; PUFA/MUFA = 2.5; MUFA/SFA = 0.6). When PUFA was fixed at a certain level (24.4 energy%), there was not a significant difference in the plasma C level between the high- and low-MUFA dietary groups (PUFA + MUFA/SFA = 4.8 and 8.4), but the higher PUFA + MUFA/SFA diet, which was high in MUFA/SFA ratio, significantly decreased the plasma HDL-C and TAG levels. However, when MUFA content was fixed at a certain level (16.4 energy%), no significant difference was observed between the two groups with different PUFA/SFA ratios of 0.2 and 4.1, but liver C level was raised in the higher PUFA/SFA diet. It appears that the PUFA/SFA ratio alone is unsuitable to predict the change of plasma C level, because a large amount of dietary MUFA may lead to an increase of plasma and liver lipids in rats. It seems that the prerequisites for keeping low plasma and liver C are (i) low MUFA/SFA ratio, (ii) high PUFA/MUFA ratio, and (iii) PUFA + MUFA/SFA ratio not to exceed 2.

Dietary Carbohydrate Type and Fat Saturation Independently Regulate Hepatic Cholesterol and LDL Metabolism in Guinea Pigs

The interactive effects of dietary fat saturation and carbohydrate (CHO) type on hepatic cholesterol and lipoprotein metabolism were investigated in guinea pigs. Guinea pigs were fed 50.8 g/100 g CHO and 7.5 g/100 g fat. The type of CHO was either sucrose or starch. The fat source was a mixture either high in lauric/myristic (SFA), oleic (MUFA), or linoleic (PUFA) acids. SFA intake resulted in a 50% higher plasma cholesterol and apo B concentrations compared with MUFA or PUFA intake ( P < 0.001). Guinea pigs from the sucrose groups had 20% higher plasma cholesterol and apo B concentrations than those from the starch group ( P < 0.01). Plasma triacylglycerol (TAG) concentrations were highest in animals fed starch and SFA. However, guinea pigs fed starch with MUFA or PUFA had lower plasma TAG than those fed sucrose with the same type of fat ( P < 0.05). Animals fed starch diets had higher concentrations of hepatic free cholesterol (FC) than those fed sucrose. Hepatic acyl CoA:cholesterol acyltransferase (ACAT) activity was higher in guinea pigs fed starch and SFA diets in agreement with higher concentrations of hepatic FC observed in these animals. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity was higher in guinea pigs fed sucrose and animals fed SFA with starch had the lowest reductase activity ( P< 0.01). Animals fed starch with MUFA or PUFA had 100% higher hepatic LDL receptor number (B max) compared with animals fed SFA. An interactive effect between CHO type and fat saturation was found because animals fed starch with MUFA had the highest and animals fed starch with SFA had the lowest LDL receptor number ( P < 0.02). These studies demonstrate that SFA and sucrose intake independently increase plasma cholesterol and TAG levels by specific alterations in hepatic cholesterol metabolism associated with production and catabolism of lipoproteins. In addition, there was a beneficial effect between MUFA, PUFA, and starch because intake of these nutrients resulted in lower plasma cholesterol and TAG levels in guinea pigs.

Effect of 347-serine mutation in apoprotein A-IV on plasma LDL cholesterol response to dietary fat.

Lipid response to dietary fat and cholesterol is, to a large extent, genetically controlled. Apoprotein (apo) A-IV has been related to fat absorption and to the activation of some of the enzymes involved in lipid metabolism. One mutation has been described in the apo A-IV gene that causes substitution of Ser for Thr at position 347. To study the influence of this mutation on the plasma LDL cholesterol (LDL-C) response in diets of various fat content and fatty acid saturation, 41 healthy male subjects were studied, 25 of whom were homozygous for the Thr allele (347Thr) and the rest who were either homozygous (n = 2) or heterozygous carriers of the Ser allele (347Ser). They consumed three consecutive diets, each of 4 weeks' duration: one rich in saturated fat (SFA diet: 38% fat, 20% saturated), a National Cholesterol Education Program (NCEP) type 1 diet (28% fat, 10% saturated), and a third rich in monounsaturated fat (MUFA diet; 38% fat, 22% monounsaturated). Carriers of the 347Ser allele presented a greater decrease in total cholesterol (-0.7 vs -0.44 mmol/L, P < .034), LDL-C (-0.62 vs -0.31 mmol/L, P < .012), and apo B (-14 vs -8 mg/dL, P < .01) levels when they were switched from the SFA to the NCEP type 1 diet than homozygous carriers of the 347Thr allele. The change from the NCEP type 1 to the MUFA diet resulted in a greater increase in total cholesterol (0.18 vs -0.05 mmol/L, P < .028) and apo B (5 vs -1 mg/dL, P < .006) levels in the 347Ser than in the 347Thr individuals. In a previous study, we demonstrated that the G-->A polymorphism at position -76 of the gene promoter of apo A-I affects the LDL-C response to dietary fat. We therefore decided to study the effect of the interaction between these mutations on this response. We found that both mutations have an additive effect on total cholesterol, LDL-C, and apo B dietary-induced changes. Our results suggest that total cholesterol and LDL-C response to dietary fat is influenced by the 347Ser mutation of apo A-IV.

Effects of high fat diets on the immune responses of Peyer's patch-immunized rats

Effects of dietary high fats on the imune responses of thoracic duct lymphocytes were investigated by comparing with phagocytic activity of alveolar macrophages (Mø) in rats immunized by intra-Peyer's patch injection of keyhole lympet hemocyanin (KLH). The oils used in this experiment were rich in either saturated fatty acid (SFA, lard oil) or polyunsaturated fatty acid (PUFA, perilla seed oil). When stimulated with mitogens (PHA, Con A and LPS), blastogenesis of thoracic duct lymphocytes was significantly greater in KLH-immunized group than saline- treated one. Degree of the enhanced response to these mitogens was much more in rats fed high PUFA diet than high SFA diet. Number of IgA-antibody presenting cells in thoracic duct lymph was increased following immunization of the Peyer's patches with KLH in rats fed PUFA diet than SFA diet. Phagocytic activity of alveolar Mø was enhanced in KLH-treated rats compared to saline-treated rats, and then after stimulation with Mø-activating factor, their activity was further increased in high PUFA diet group than in high SFA diet one. These results suggest that high-dietary PUFA in Peyer's patchimmunized rats is capable of more increasing the immune responses of thoracic duct lymphocytes and sequentially of enhancing phagocytic activity of alveolar Mø compared to high SFA.

Influence of dietary fat quantity and composition on insulin binding to rat intestine.

It is presently recommended that the general US population reduce the consumption of dietary lipid in order to reduce the risk of several chronic diseases, although the mechanism(s) through which dietary factors alter cellular function remain unclear. Dietary lipid composition has been shown to alter the plasma membrane lipid composition of adipocytes, muscle and other tissues. These changes in membrane lipid composition have been correlated with altered insulin receptor binding and signal transduction. Insulin receptors are present on mucosal cells of the intestinal tract, although their role in this tissue is not fully understood. We have fed rats diets containing 6, 31.4 or 76% of calories from lard (Protocol 1) and found insulin binding to be increased in the duodenum and decreased in the colon of rats fed the high-fat diet. Additionally, we compared diets containing either 12 or 37.6% of calories from beef tallow (saturated fatty acids or SFA) or corn oil (polyunsaturated fatty acids or PUFA; Protocol 2) and found insulin binding in the jejunum to be significantly decreased by a low SFA or high PUFA diet relative to the low PUFA diet. These results suggest that intestinal insulin receptors are responsive to dietary lipid quantity and quality which may have implications as to the role of dietary factors in modifying nutrient transport and/or risk of intestinal disease.

Quantity and saturation degree of dietary fats as modulators of oxidative stress and chemically‐induced liver tumours in rats

Male rats were fed, from weaning onwards, either 2, 12.5 or 25% sunflower seed oil (polyunsaturated fatty acids, PSA) or lard (saturated fatty acids, SFA) and from the age of 15 weeks subgroups were given N-nitrosodimethylamine (NDMA) for 30 weeks. Blood levels of lipids were assayed and during the study exhaled ethane was measured as an index of in vivo lipid peroxidation (LPO). At the age of 50 weeks, rats were killed and livers were analysed for tumours. PSA diets decreased plasma cholesterol and triglyceride concentrations vs. respective SFA diet; NDMA administration did not affect plasma cholesterol but enhanced triglyceride concentration. NDMA markedly enhanced LPO. An increase in dietary fat content from 2 to 25% enhanced ethane exhalation, more in rats fed PSA than the SFA diet. In the 25% PSA group, indomethacin in the diet strongly inhibited LPO. Prevalence of liver haemangiosarcomas increased from 42% to 80% (p less than 0.05) in NDMA-treated animals when PSA increased from 2 to 25%; in the group having a 25% PSA diet containing indomethacin, the NDMA-induced tumour incidence was reduced to 64%. In NDMA-treated rats fed SFA diets the prevalence of haemangiosarcoma increased from 43% (2% fat) to 67% (25% fat). The data show that NDMA modifies plasma lipids and increases LPO. The quantity and saturation degree of fats altered the frequency of chemically-induced tumours and modified LPO. As an index of free radical reactions, LPO may have an important role in carcinogenesis. Dietary fat thus appears to promote carcinogenesis through mechanisms that involve LPO.