Saturated Research Articles

Dietary fat saturation, but not the feeding state, modulates rates of cholesterol esterification in normolipidemic men

To determine whether the rates of cholesterol esterification in normal individuals are affected by diets differing in fats, nine men were randomly assigned to three groups receiving a diet rich in monounsaturated (MONO), polyunsaturated (POLY), or saturated (SAT) fat for 2 weeks using a crossover design. Subjects drank a dose of deuterium oxide, and the fractional esterification rate (FER) was calculated during fed and unfed periods. Total esterified cholesterol was calculated as the product of the FER and pool size, the latter obtained from a decay curve following injection of [4- 14C]-cholesterol. The POLY diet produced the lowest serum cholesterol concentration and the SAT diet the highest ( P < .001). For cholesterol ester (CE) deuterium enrichment, an interaction was noted between diet and time ( P < .01). The FER was greater ( P < .003) in subjects fed the POLY diet versus either of the other diets, although the amount of esterified cholesterol produced, expressed as either milligrams per day ( P < .103) or milligrams per kilogram of body weight per day ( P < .100), did not differ among groups. No effect of the feeding state was found for either the FER ( P < .187) or total esterified cholesterol expressed as milligrams per day ( P < .146) or milligrams per kilogram of body weight per day ( P < .128). The results suggest that the diet fat type, but not the feeding state, may be responsible for serum esterified cholesterol concentrations.

Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation

Previous studies have shown that the A to G transition occurring at position −75 bp upstream of the transcriptional start site in the human apolipoprotein A-I gene may affect plasma high density lipoprotein cholesterol (HDL-C) levels and low density lipoprotein cholesterol (LDL-C) response to changes in amount of dietary fat. We have examined the response to dietary fat saturation as a function of this mutation in 50 men and women. Subjects were first fed a saturated (SAT) fat diet (35% fat, 17% SAT) for 28 days, followed by a diet rich in monounsaturated fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet rich in polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days. All meals were prepared and consumed at the study sites. Lipoproteins were measured at the end of each diet period. The allele frequency for the A allele was 0.13. Subjects carrying the A allele had higher plasma cholesterol, LDL-C and triglyceride levels than those homozygotes for the G allele. As compared to the SAT diet, a PUFA diet induced significantly greater plasma total ( P=0.003) and LDL-C decreases ( P=0.001) in G/A women (−1.62 and −1.32 mmol/l, respectively) than in G/G subjects (−0.87 and −0.74 mmol/l for plasma and LDL-C, respectively). Multiple regression analysis demonstrated that in women, the variability in LDL-C response from a diet rich in SAT fat to a diet rich in PUFA was primarily due to LDL-C levels (during the SAT phase), accounting for 55.1% of the variance, waist to hip ratio (W/H; 11.4%) and the G/A polymorphism (10%). Whereas in men the major determinant of this response was smoking (21.4%). In conclusion, the G/A polymorphism appears to have a small but significant effect on plasma LDL-C responsiveness to changes in dietary fat saturation specially in women.

Vitamin C level and dietary fat saturation alter hepatic cholesterol homeostasis and plasma LDL metabolism in guinea pigs

This study addressed the independent and interactive effects of vitamin C status and dietary fat saturation on hepatic cholesterol and LDL metabolism in guinea pigs. Animals were fed adequate (500 mg/kg) or marginal (50 mg/kg) vitamin C with diets high in polyunsaturated (POLY), monounsaturated (MONO), or saturated (SAT) fatty acids during 6 weeks. Plasma cholesterol, triacylglycerol (TAG), and apo B concentrations were higher in animals fed vitamin C-deficient compared with Vit C-adequate diets ( P < 0.02). SAT fat intake also resulted in more elevated plasma cholesterol and apo B concentrations ( P < 0.001). The susceptibility of LDL to oxidation was highest in animals fed POLY diets and marginal levels of vitamin C ( P < 0.001). Intake of adequate levels of vitamin C significantly reduced TBARS formation by 64% in animals fed POLY diets indicating an interactive effect between POLY fat intake and the level of vitamin C. Hepatic Acyl CoA cholesterol acyltransferase (ACAT) activity was higher by SAT fat intake ( P < 0.01) and marginal intake of vitamin C ( P < 0.05), whereas cholesterol 7α-hydroxylase activity was lower in vitamin C-deficient groups ( P < 0.01). LDL fractional catabolic rates (FCR) were 42 to 67% faster and LDL apo B flux slower in animals fed POLY and MONO diets compared with the SAT group ( P < 0.001). Animals fed marginal levels of vitamin C had higher LDL apo B flux ( P < 0.05). These data suggest that the higher plasma LDL concentrations induced by SAT diets are caused by both slower LDL FCR and higher LDL apo B flux, whereas the hypercholesterolemia and hypetriglyceridemia induced by vitamin C deficiency with POLY and MONO diets is mainly caused by alterations in hepatic cholesterol homeostasis, which result in higher LDL apo B flux.

Diet Fat Saturation and Feeding State Modulate Rates of Cholesterol Synthesis in Normolipidemic Men ,

To determine whether diets differing in fats affect cholesterol synthesis in normal individuals, nine men were randomly assigned to three groups that received three diets in a crossover design for 2 wk. Diets were either monounsaturated (MONO), polyunsaturated (POLY), or saturated (SAT). Subjects then drank a dose of deuterium oxide, and unesterified cholesterol fractional synthesis rates (FSR) were calculated during consecutive fed and unfed periods. Absolute synthesis was calculated as the product of FSR and pool size, the latter obtained from a decay curve following a [4-14C]cholesterol injection. Serum cholesterol concentrations varied with each diet consumed (P = 0.001); the SAT diet produced the highest and the POLY diet the lowest. Triglyceride concentrations were highest when subjects consumed the SAT diet and lowest with the POLY diet (P = 0.03); values obtained with the MONO diet did not differ significantly from those seen otherwise. HDL cholesterol concentrations were lowest when the SAT diet was consumed, highest when subjects were fed the MONO diet (P = 0.05), and midway but not significantly different with the POLY diet. Cholesterol FSR were greater when subjects consumed (P = 0.001) rather than not, and FSR during 12-h periods were greater (P = 0.045) when subjects ate the POLY diet rather than the SAT diet. Absolute synthesis was also greater (P = 0.04) when subjects were fed, but did not differ with fat type (P = 0.789). Results suggest that cholesterol synthesis is greater when men are fed than when they are not fed, and reduced synthesis is not responsible for the effect of different fats on cholesterol concentrations.

Plasma cholesteryl ester synthesis, cholesteryl ester transfer protein concentration and activity in hypercholesterolemic women: effects of the degree of saturation of dietary fatty acids in the fasting and postprandial states

Hypercholesterolemic women ( n = 19) sequentially maintained on a long-term saturated (SAT) or a polyunsaturated (PUFA) fatty acid-rich diet, respectively, were studied in the fasting state and after a meal rich in SAT or PUFA. When apo B-containing lipoprotein was excluded from plasma the in vitro HDL- 14C-cholesterol esterification rate was identical for the saturated (SAT) and polyunsaturated (PUFA) fatty acid diets, and did not increase during the postprandial period. Rates of transfer of 14C-cholesteryl ester to apo B-containing lipoproteins from HDL were also similar for both diets in the fasting state and increased to the same extent in the postprandial period in parallel with the rise in plasma triglycerides. When transfer data were related to the plasma concentration of apo B, the gain of cholesteryl ester by the triglyceride-containing particles (VLDL + LDL) also increased in the postprandial period to a similar extent for both diets. Cholesteryl ester transfer protein (CETP) concentration measured by radioimmunoassay was similar during both experimental diets, although greater in the postprandial period for the PUFA diet. The rate limiting factor for CETP-mediated transfer of HDL-derived cholesteryl ester (CE) was the plasma triglyceride concentration, that is, the content of triglycerides per lipoprotein particle and the quantity of TG-containing particles (VLDL + LDL). In contrast, the fatty acid composition of these particles had less effect on CETP-mediated CE transfer.

Diets enriched in unsaturated fatty acids enhance apolipoprotein A-I catabolism but do not affect either its production or hepatic mRNA abundance in cynomolgus monkeys

To determine the mechanisms whereby dietary fatty acids influence high density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations, ten cynomolgus monkeys were fed each of three experimental diets enriched in saturated (SAT), monounsaturated (MONO), or polyunsaturated (POLY) fatty acids in a crossover design consisting of three 13-week periods, with each animal serving as its own control. Each diet contained 30% of energy as fat with 0.22 mg cholesterol/kcal and differed solely by the isocaloric substitution of fatty acids as 18% of total energy calories. The replacement of dietary saturated fatty acids with either monounsaturated or polyunsaturated fatty acids, respectively, resulted in significant reductions of plasma total cholesterol ( − 17%; − 30%), HDL cholesterol ( − 32%; − 41%), and apo A-I (− 37%; − 44%) concentrations, while no significant differences were noted in. plasma lipid or apo A-I concentrations when the MONO and POLY phases were compared. Although the MONO and POLY diets were similar in their effects on plasma lipids and apolipoproteins, the HDL of monkeys fed the POLY diet, as compared with either the SAT or the MONO diets, contained more cholesteryl ester and phospholipid but less total protein, resulting in a significantly lower total lipid to protein constituent ratio. Metabolic experiments revealed that the significantly lower plasma apo A-I concentrations observed during both the MONO and POLY phases relative to SAT were directly attributable to enhanced HDL apo A-I catabolism. Conversely, neither HDL apo A-I production rates nor hepatic apo A-I mRNA concentrations were significantly affected by dietary fatty acid perturbation in this study. Taken together, these data indicate that fractional catabolic rate is the predominant mechanism by which dietary fatty acids differentially modulate circulating concentrations of HDL apo A-1 in this species when all other dietary variables are held constant.

N-3 and N-6 fatty acids modulate the inotropic response to calcium in hypothyroid rat papillary muscle.

The calcium sensitivity of papillary muscles was enhanced at low [Ca2+] in euthyroid rats fed a diet enriched in n-3 fatty acids compared to rats fed diets high in n-6 and saturated (SAT) fatty acids. At the same time, the maximum developed tension was 44% lower in animals fed the n-3 diet compared to those fed the n-6 diet and 62% lower than the rats fed the SAT diet. In hypothyroid animals fed the n-3 diet, the inotropic response to added Ca2+ was only 60% of that in euthyroid controls and 50 and 65% of euthyroid controls in n-6 and SAT diet-fed animals, respectively. Although the response was again lower in n-3-fed animals, the differences among the diet treatments were not as great as those seen in euthyroid animals, and there were no apparent diet-dependent differences in sensitivity to Ca2+ in hypothyroid animals. The potency of the calcium-channel blocker nifedipine was diet-dependent in euthyroid animals, with the order of decreasing sensitivity being n-3 > n-6 > SAT. Papillary muscles were not as sensitive to nifedipine in hypothyroid animals, although n-3-fed animals again showed the greatest inhibition of tension development. On the other hand, nitrendipine-binding affinity was not different among euthyroid and hypothyroid animals fed the n-6 diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Antioxidant enzyme activities in the lymphoid organs and muscles of rats fed fatty acids-rich diets subjected to prolonged physical exercise-training

Rats weighing 45–50 g were fed 3 diets for 8 wk: a balanced control diet (CD) consisting of 4% fat (polyunsaturated/saturated fatty acids [P/S] ratio 2.9/1) and two fat-rich diets: polyunsaturated (UD)—P/S 7.6/1 and saturated (SD) P/S 0.3/1. After 8 wk feeding on the respective diets, rats were subjected to swimming for 90 min at 30°C daily, 5 d/wk for 8 wk. At the end of this period, the rats were killed and the lymphoid organs (LO—thymus, spleen, and mesenteric lymph nodes) and muscles (soleus and gastrocnemius) removed for the measurement of TBARs (Thiobarbituric Acid Reactant Substances) content and of the activities of antioxidant enzymes (CuZn- and Mn-Superoxide dismutase.—SOD—, catalase, and glutathione peroxidase). To evaluate the changes in the sites of generation of reducing equivalents involved in the formation of free radicals, the activities of citrate synthase and glucose-6-phosphate dehydrogenase were measured. The exercise-training clearly modified the enzyme activities and TBARs content of the lymphoid organs and skeletal muscles, but this effect was dependent upon the diet given to the rats. However, fatty acid rich diets had presented a more pronounced effect on the studied aspects than did physical activity. Although one could expect a summatory effect of polyunsaturated fatty acid-rich diet and exercise-training, swimming increased the activities of CuZn- and Mn-SOD in almost all tissues from the elevated level promoted by fat-rich diets.

Dietary saturated (SAT) compared to polyunsaturated (PUFA) fatty acids accelerates the CETP-mediated, HDL-cholesteryl ester transfer rate to apo B-containing LP in the alimentary state

Dietary saturated (SAT) compared to polyunsaturated (PUFA) fatty acids accelerates the CETP-mediated, HDL-cholesteryl ester transfer rate to apo B-containing LP in the alimentary state

Effects of dietary fat saturation on plasma lipoprotein(a) and hepatic apolipoprotein(a) mRNA concentrations in cynomolgus monkeys

Plasma lipoprotein(a) (Lp(a)) concentration is an independent risk factor for the development of premature coronary artery disease. Although the majority of available data indicates that circulating Lp(a) levels are under strict genetic regulation, there is some evidence that this parameter may be subject to dietary modification as well. The effects of dietary fat saturation on plasma Lp(a) levels and hepatic apolipoprotein(a) (apo(a)) mRNA abundance were examined in ten unrelated cynomolgus monkeys which were fed each of three experimental diets enriched in saturated (SAT), monounsaturated (MONO), or polyunsaturated (POLY) fatty acids in a crossover design consisting of three 13-week periods. Each diet contained 30% of calories as fat with 0.1% dietary cholesterol by weight and differed solely by the isocaloric substitution of fatty acids as 60% of total fat calories. The mean Lp(a) level for these animals during the SAT diet (13.4 ± 2.4 mg/dl) was significantly greater as compared with those observed during the MONO (8.6 ± 2.2 mg/dl, P < 0.0003) and POLY (9.3 ± 2.1 mg/dl, P < 0.002) diets, while the difference noted between the MONO and POLY diets was nonsignificant. Hepatic apo(a) mRNA abundance was decreased in these animals during the MONO diet relative to both the SAT and POLY diets, with only the difference between the SAT and MONO diets achieving statistical significance ( P < 0.02). Our data demonstrate that the substitution of dietary SATs with either MONOs or POLYs result in significant reductions of Lp(a) levels in these monkeys. However, only the MONO diet significantly decreased hepatic apo(a) mRNA levels relative to the SAT diet, suggesting that dietary MONOs and POLYs may differ in the manner by which they regulate plasma Lp(a) levels.