Effects Of Dietary Fat Saturation Research Articles

Impact of saturated compared with unsaturated dietary fat on insulin sensitivity, pancreatic β-cell function and glucose tolerance: a systematic review and meta-analysis of randomized, controlled trials

BackgroundThe impact of the dietary fat type on type 2 diabetes (T2D) remains unclear. ObjectivesWe aimed to evaluate the effects of replacing dietary saturated fatty acids (SFA) with mono- or poly-unsaturated fatty acids (MUFA and PUFA, respectively) on insulin sensitivity, pancreatic β-cell function, and glucose tolerance, as surrogate endpoints for T2D. MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials that replaced ≥5% of total energy intake provided by SFA with MUFA or PUFA and reported indexes of insulin sensitivity, β-cell function, and/or glucose tolerance. We searched MEDLINE, Scopus, and the Cochrane Library (CENTRAL) up to 9 January, 2023. Eligible interventions had to be isocaloric, with no significant difference in other macronutrients. Data were synthesized using random-effects model meta-analysis. ResultsOf 6355 records identified, 10 parallel and 20 crossover trials with 1586 participants were included. The mean age of the participants was 42 years, 47% were male, mean body mass index (BMI; in kg/m2) was 26.8, median baseline fasting glucose was 5.13 mmol/L, and the median duration of interventions was 5 weeks. Replacing SFA with MUFA or PUFA had no significant effects on insulin sensitivity [standardized mean difference (SMD) SFA compared with MUFA: 0.01, 95% confidence interval (CI): −0.06 to 0.09, I2 = 0% and SMD SFA compared with PUFA: 0, 95% CI: −0.15 to 0.14, I2 = 0%]. Replacing SFA with MUFA did not significantly impact the β-cell function, evaluated by the disposition index (mean difference: −12, 95% CI: −158 to 133, I2=0%). Evidence on glucose tolerance (SFA compared with MUFA or PUFA) and on β-cell function when SFA were replaced with PUFA was scant. ConclusionsShort-term substitution of saturated with unsaturated fat does not significantly affect insulin sensitivity nor β-cell function (the latter in the SFA compared with MUFA comparison). Future studies are needed to elucidate longer term effects of dietary fat saturation on glucose homeostasis. This trial was registered at PROSPERO as CRD42020178382.

Dietary Fat Saturation and Endurance Exercise Alter Lipolytic Sensitivity of Adipocytes Isolated from Yucatan Miniature Swine , ,

This study examined the effects of dietary fat saturation and endurance exercise on lipolytic sensitivity of adipocytes isolated from Yucatan miniature swine. Twenty-four female swine had free access to a high fat diet with a polyunsaturated to saturated fat ratio (P:S) of 0.3 or 1.0, and were treadmill-exercised or remained sedentary. After 3 months, biopsies were taken, adipocytes were isolated and lipolytic activity was determined. Adipocytes were incubated with adenosine deaminase followed by epinephrine, isoproterenol, or epinephrine plus phenylisopropyladenosine, and glycerol release was measured. Backfat thickness was measured by ultrasonography. Our findings revealed that 1) adipocytes from 1.0 P:S diet-fed swine released 30% more glycerol than adipocytes from 0.3 P:S diet-fed swine when stimulated by 1 micromol/L isoproterenol; 2) adipocytes from exercised swine released 45% more glycerol than adipocytes from sedentary swine when stimulated by 1 micromol/L epinephrine; 3) body weight of exercised swine was significantly lower than sedentary swine; and 4) backfat thickness was less in exercised swine than in sedentary swine (2.39 vs. 2.95 cm, P = 0.002). We conclude that ad libitum consumption of diet with a P:S of 1.0, combined with endurance exercise, increases lipolytic sensitivity, lowers body weight gain, and reduces fat accumulation in female Yucatan miniature swine.

Effects of dietary fat saturation on fatty acid composition and gene transcription in different tissues of Iberian pigs

The effect of two diets, respectively enriched with SFA (S) and PUFA (P), on FA tissue composition and gene expression was studied in fattened Iberian pigs. The FA composition of adipose, muscular and liver tissues was affected by dietary treatment. S group showed higher MUFA and MUFA/SFA ratio and lower PUFA and n−6/n−3 ratio than P group in all analyzed tissues. In muscle and liver the extracted lipids were separated into neutral lipids and polar lipid fractions which showed significantly different responses to the dietary treatment, especially in liver where no significant effect of diet was observed in NL fraction. The expression of six candidate genes related to lipogenesis and FA oxidation was analyzed by qPCR. In liver, stearoyl CoA desaturase (SCD), acetyl CoA carboxylase alpha (ACACA) and malic enzyme 1 (ME1) genes showed higher expression in S group. SCD, ACACA, ME1, and fatty acid synthase (FASN) gene expression levels showed a wide variation across the tested tissues, with much higher expression levels observed in adipose tissue than other tissues. Tissue FA profile and gene expression results support the deposition of dietary FA, the lipogenic effect of dietary saturated fat in liver and the employment of saturated dietary fat for endogenous synthesis of MUFA in all the analyzed tissues.

Interactions between genotype, dietary fat saturation and vitamin A concentration on intramuscular fat content and fatty acid composition in pigs

The effect of dietary fat saturation (dFat) and dietary vitamin A (dVitA) level (0 IU vs. 100,000 IU) on performance, carcass characteristics and fatty acid composition in the offspring of two terminal sires: Duroc (DU) and Landrace × Large White (LD × LW) was studied. In the inner backfat layer, the DU-sired pigs had higher C16:0 proportion ( P < 0.05) and tended ( P < 0.07) to have higher total saturated fatty acids (SFA) and lower C18:1 n-9 proportions than LD × LW-sired pigs. An interaction sire line × dVitA was observed for intramuscular fat (IMF) content ( P < 0.005). The effect of supplementation with the high dVitA level in DU-sired pigs was associated with a 20% increase in IMF while no effect was observed in LD × LW pigs. Fatty acid pattern was affected by dFat and sire line. In the inner backfat layer, LD × LW-sired pigs receiving the low dVitA level increased C18:0 proportions by 8% in comparison to animals receiving the high dVitA, whereas in DU-sired pigs the effect of vitamin A was opposite. It is concluded that the effect of dFat and dVitA concentration on IMF content and fatty acid profile of subcutaneous backfat and IMF is variable according to pig genotype.

Effects of Feed Restriction and Dietary Fat Saturation on Performance and Serum Thyroid Hormones of Broiler Chickens

This experiment carried out to study the effects of dietary fat saturation on performance and serum thyroid hormones of broilers under free or skip a day nutrition at 18-28 days of age. We used 720 male Ross 308 broiler chickens in a completely randomized design with a 2*4 factorial arrangement with 3 replicate and 30 chicks for each replicate. Experiment factors were: 1skip a day or free feeding at days 10-28 of age and, 2diets with different unsaturated to saturated fatty acid ratios (2, 3.5, 5 and 6.5) formulated using different levels of sunflower oil and tallow. At 28 and 42 days of age, weight gain and feed consumption recorded and blood samples were taken. SAS software used for Variance analysis and means comparing. Skip a day nutrition at days 18-28 of age significantly reduced feed intake and weight gain and increased feed conversion, But free nutrition at days 29-42 of age removed this differences. At day 28, diet with unsaturated to saturated ratio of 6.5 significantly reduced feed intake and weight gain and increased feed conversion. At day 42 of age dietary fat type didn’t have any significant effect on feed intake and weight gain but altered feed conversion as a manner same to day 28 of age. Skip a day nutrition significantly decreased T3 and increased T4 levels at day 28 of age but this effects were disappeared after re-feeding at day 42 of age. This survey showed that feed restriction didn’t affect bird’s ability to utilize fats with different degrees of saturation. Fat type and feed restriction affect broilers performance separately without any interaction. Dietary fat saturation didn’t have any significant effect on serum thyroid hormones levels, while feed restriction have a pronounce effect.

Effect of dietary fat saturation on lipid metabolism, arachidonic acid turnover and peritoneal macrophage oxidative stress in mice

We investigated the effects of a saturated fat diet on lipid metabolism and arachidonic acid (AA) turnover in mouse resident peritoneal macrophages. The pro-oxidative effect of this diet was also studied. Female C57BL/6 mice were weaned at 21 days of age and assigned to either the experimental diet containing coconut oil (COCO diet), or the control diet containing soybean oil as fat source (10 mice per group). The fat content of each diet was 15% (w/w). Mice were fed for 6 weeks and then sacrificed. The concentration of total lipids, triglycerides, (LDL+VLDL)-cholesterol, thiobarbituric acid-reactive substances (TBARS) and reduced glutathione were increased in the plasma of mice fed the COCO diet, without changes in phospholipid or total cholesterol concentrations compared to control. The concentrations of total cholesterol, free and esterified cholesterol, triglycerides, and TBARS were increased in the macrophages of COCO-fed mice, while the content of total phospholipids did not change. The phospholipid composition showed an increase of phosphatidylcholine and a decrease of phosphatidylethanolamine. The [3H]-AA distribution in the phospholipid classes showed an increase in phosphatidylcholine and phosphatidylethanolamine. Incorporation of [3H]-cholesterol into the macrophages of COCO-fed mice and into the cholesterol ester fraction was increased. The COCO diet did not affect [3H]-AA uptake but induced an increase in [3H]-AA release. The COCO diet also enhanced AA mobilization induced by lipopolysaccharide. These results indicate that the COCO diet, high in saturated fatty acids, alters the lipid metabolism and AA turnover of peritoneal macrophages in female mice and also produces a significant degree of oxidative stress.

Dietary fat saturation and gender/hormonal status modulate plasma lipids and lipoprotein composition

Male, female and ovariectomized (to mimic menopause) guinea pigs were fed a saturated (SFA) or a polyunsaturated (PUFA) fat diet for 4 weeks to determine the effects of dietary fat saturation on lipoprotein levels and composition and to assess whether gender and hormonal status modulate the cholesterolemic response. Both diets contained 15g/100 g fat and 0.04 g/100 g cholesterol and were identical in composition except for the type of fat. The SFA diet contained 50% saturated fat (25% lauric + myristic fatty acids), 25% PUFA and 25% monounsaturated fatty acids while the PUFA diet had 50% PUFA (linoleic acid), 25% monounsaturated and 25% SFA fatty acids. Plasma LDL cholesterol (LDL-C) was an average 21% lower in guinea pigs fed PUFA compared to those fed SFA (P < 0.05). In addition, ovariectomized guinea pigs, both in the SFA and PUFA groups, had 20–33% higher LDL-C than either males or females (P < 0.01). VLDL cholesterol was 70% higher in the PUFA-fed animals (P < 0.0001). A gender effect was observed in plasma HDL cholesterol (HDL-C) with females and ovariectomized guinea pigs having 30–42% higher HDL-C than males (P < 0.01). LDL susceptibility to oxidation was not affected by dietary fat saturation or gender. In contrast, VLDL and LDL composition were significantly influenced by diet and gender. VLDL particles were larger in size in guinea pigs fed the SFA diets (P < 0.01) while LDL particles were larger in female guinea pigs (P < 0.001). Hepatic lipids were influenced by the interaction between diet and group. Hepatic cholesterol (P < 0.01) and TAG concentrations (P < 0.0001) were highest in female guinea pigs fed the PUFA diet. Since the liver is the major site of lipoprotein synthesis and catabolism, these results suggest that not only diet but also gender may play a major role in determining the composition and size of lipoproteins.

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 dietary fat saturation on LDL oxidation and monocyte adhesion to human endothelial cells in vitro.

Forty-two healthy men and women were subjected to four consecutive dietary periods differing in the fat content of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (n-6) [PUFA(n-6)] and (n-3) [PUFA(n-3)]. Plasma lipids, vitamin E, and in vitro LDL oxidation were examined during each period. Adhesion of human monocytes to cultured human endothelial cells was used as a functional test to identify differences in the biological properties of LDL from each dietary period. Consumption of an SFA-rich diet resulted in higher LDL cholesterol (4.06 +/- 0.85 mmol/L, P < .05) than did consumption of MUFA- (3.59 +/- 0.75 mmol/L), PUFA(n-6)- (3.44 +/- 0.77 mmol/L), or PUFA(n-3)- (3.31 +/- 0.8 mmol/L) rich diets. HDL cholesterol was lower during both PUFA-rich diets (1.24 +/- 0.28 and 1.27 +/- 0.28 mmol/L for n-6 and n-3, respectively) than during the SFA-(1.32 +/- 0.36 mmol/L) and MUFA- (1.32 +/- 0.34 mmol/L) rich diets. LDL resistance to copper-induced oxidation, expressed as lag time, was highest during the MUFA-rich diet (55.1 +/- 7.3 minutes) and lowest during the PUFA(n-3)- (45.3 +/- 7 minutes) and SFA- (45.3 +/- 6.4 minutes) rich diets. LDL induction of monocyte adhesion to endothelial cells was lower during the MUFA-rich diet than the other periods. The highest monocyte adhesion was obtained during the PUFA(n-3) and SFA dietary periods. In conclusion, an MUFA-rich diet benefits plasma lipid levels compared with an SFA-rich diet. Furthermore, this diet results in an increased resistance of LDL to oxidation and a lower rate of monocyte adhesion to endothelial cells than the other dietary fats examined.

Regulation of guinea pig very low density lipoprotein secretion rates by dietary fat saturation.

We investigated the effects of dietary fat saturation on very low density lipoprotein (VLDL) production in guinea pigs fed semipurified diets containing 15% (w/w) fat, either corn oil (CO, 58% linoleic acid), lard (LA, 42% oleic and 24% palmitic acids) or palm kernel oil (PK, 52% lauric and 18% myristic acids) for 4 weeks. Animals were given an intravenous injection of Triton WR 1339 to block VLDL catabolism and rates of VLDL triacylglycerol (TAG) and apolipoprotein (apo) B secretion were measured over time. Plasma TAG concentrations increased linearly for 8 h (r = 0.99) and VLDL-TAG secretion rates were significantly higher (P < 0.01) in guinea pigs fed LA (72.7 +/- 14.7 mg/kg-h, n = 12) compared to animals fed PK (55.4 +/- 13.4 mg/kg-h, n = 12) or CO (48.6 +/- 17.5 mg/kg-h, n = 15). VLDL apoB secretion rates were highest in PK-fed animals (3.1 +/- 1.8 mg/kg-h) compared to guinea pigs fed LA (1.5 +/- 0.8 mg/kg-h) or CO (1.1 +/- 0.6 mg/kg-h) diets (P < 0.005). Concurrent with analysis of VLDL secretion, turnover of 125I-labeled LDL was measured. Low density lipoprotein (LDL) fractional catabolic rates were not altered by Triton treatment and LDL apoB specific radioactivity (cpm/microgram) did not change over time indicating that: a) the Triton blockage of VLDL catabolism was complete, and b) there was no direct secretion of LDL by the liver. These data demonstrate that intake of lard increases the rate of VLDL-triacylglycerol secretion and that nascent VLDL particles from the lard and corn oil diet groups have the same relative triacylglycerol content, whereas palm kernel oil intake increases secretion of VLDL particles which have a reduced triacylglycerol content. These results demonstrate that dietary fat chain length and saturation have specific effects on VLDL secretion rates affecting both particle number and composition.

Dietary Fat Saturation and Endurance Exercise Alter Lipolytic Sensitivity of Adipocytes Isolated from Yucatan Miniature Swine , ,

This study examined the effects of dietary fat saturation and endurance exercise on lipolytic sensitivity of adipocytes isolated from Yucatan miniature swine. Twenty-four female swine had free access to a high fat diet with a polyunsaturated to saturated fat ratio (P:S) of 0.3 or 1.0, and were treadmill-exercised or remained sedentary. After 3 months, biopsies were taken, adipocytes were isolated and lipolytic activity was determined. Adipocytes were incubated with adenosine deaminase followed by epinephrine, isoproterenol, or epinephrine plus phenylisopropyladenosine, and glycerol release was measured. Backfat thickness was measured by ultrasonography. Our findings revealed that 1) adipocytes from 1.0 P:S diet-fed swine released 30% more glycerol than adipocytes from 0.3 P:S diet-fed swine when stimulated by 1 micromol/L isoproterenol; 2) adipocytes from exercised swine released 45% more glycerol than adipocytes from sedentary swine when stimulated by 1 micromol/L epinephrine; 3) body weight of exercised swine was significantly lower than sedentary swine; and 4) backfat thickness was less in exercised swine than in sedentary swine (2.39 vs. 2.95 cm, P = 0.002). We conclude that ad libitum consumption of diet with a P:S of 1.0, combined with endurance exercise, increases lipolytic sensitivity, lowers body weight gain, and reduces fat accumulation in female Yucatan miniature swine.

Effects of dietary fat saturation on plasma lipoproteins and Lp(a) levels

Effects of dietary fat saturation on plasma lipoproteins and Lp(a) levels

Effects of dietary fat saturation on platelet aggregation

Effects of dietary fat saturation on platelet aggregation

Differential effect of dietary fat saturation and cholesterol on hepatic apolipoprotein gene expression in rats

The effects of dietary cholesterol and fat saturation on hepatic apolipoprotein A-I, A-I1, A-IV, B, C-I, C-III, E and LDL receptor mRNA levels were studied in male rats. Animals were maintained for 2 months on a high fat diet (40% w/w) containing 0.1% cholesterol. Two groups of control animals received either chow diet or chow plus 0.1% cholesterol, while experimental groups received as their fat supplement coconut, corn or olive oil. Olive oil fed animals had higher levels of hepatic apo A-I than the control cholesterol group (1.6 ± 0.3 vs. 0.8 ± 0.2). Apo E mRNA levels were 50% and 72% higher in animals consuming the saturated (coconut) and unsaturated (corn and olive) fat diet than the control cholesterol group. Apo B and apo C-I mRNA levels were not affected by the experimental conditions. Apo A-IV mRNA increased between 66% and 127% in groups in which cholesterol was present. LDL receptor mRNA increased 2 times in the corn fed group compared with the control groups. These results indicate that the expression of genes coding for products involved in lipoprotein metabolism have a differential susceptibility to dietary fat saturation and cholesterol.

Interaction of dietary fat saturation and cholesterol level on cholesterol synthesis measured using deuterium incorporation.

To examine interactive effects of dietary fat saturation and cholesterol level on serum lipids and de novo cholesterogenesis, moderately hypercholesterolemic subjects were fed solid-foods diets containing 30% fat (80 mg C.1000 Kcal-1) in which 2/3 fat was either corn oil or beef tallow, with and without 120 mg C.1000 Kcal-1, for 5 wk. At the end of each diet period, subjects were given deuterium (D) oxide orally and de novo cholesterol synthesis was measured over 24 h from D incorporation into cholesterol as fractional synthesis rates (FSR) and absolute synthetic rate (ASR) into the rapid exchangeable cholesterol pool. Plasma total and low density lipoprotein levels were elevated (P < 0.01) with both beef tallow and cholesterol feeding. High density lipoprotein (HDL) levels were not influenced by fat saturation or cholesterol level; however, HDL was higher with addition of cholesterol to corn oil versus beef tallow (P < 0.02). Plasma triglycerides were higher (P < 0.02) with beef tallow feeding but were not influenced by cholesterol level. FSR was increased (P < 0.02) by feeding corn oil, versus beef fat, but not by dietary cholesterol level. Calculated cholesterol pools sizes did not differ across groups; however, ASR was also elevated with corn oil versus beef tallow feeding (P < 0.02). Results indicate that corn oil feeding lowers circulating cholesterol by mechanisms other than reduced synthesis, and that cholesterol at the level of supplementation used is not associated with feedback inhibition of cholesterogenesis. However, with the exception of HDL levels, dietary fat saturation and cholesterol levels do not interactively influence circulating lipoprotein cholesterol levels and cholesterol synthesis.

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.

Regulation of hepatic LDL metabolism in the guinea pig by dietary fat and cholesterol.

Studies were carried out to determine the independent and interactive effects of dietary fat and cholesterol on the regulation of hepatic apoB/E receptor expression and its relationship to hepatic cholesterol concentrations and low density lipoprotein (LDL) particle characteristics. Guinea pigs were fed 15% (w/w) fat diets (lard, olive oil, or corn oil) with cholesterol levels corresponding to absorbed intakes of 6 (basal), 50, 100, or 200% endogenous cholesterol synthesis. Guinea pigs maintained stable plasma cholesterol levels until cholesterol intake equaled or exceeded endogenous synthesis (P < 0.001). Fat type independently affected plasma total and LDL cholesterol levels such that lard > corn oil, with olive oil being intermediate (P < 0.05). Hepatic membrane apoB/E receptor number (Bmax) decreased as dietary cholesterol increased (P < 0.001) without an independent effect of dietary fat saturation. Bmax values were significantly correlated with plasma LDL cholesterol levels (r = -0.632), and with hepatic free (r = 0.527) and esterified cholesterol (r = -0.512) concentrations, which were both increased with dietary cholesterol (P < 0.001). Significant interactions between dietary fat type and cholesterol mediated the extent of hepatic free and esterified cholesterol accumulation. Dietary fat and cholesterol interactions also contributed to changes in LDL particle composition and peak density. The results of these studies do not support the thesis that dietary cholesterol-mediated suppression of apoB/E receptor expression is ameliorated by intake of polyunsaturated fatty acids. Dietary fat type and cholesterol amount interactively affect hepatic cholesterol concentrations and LDL composition and size, which in part determine plasma LDL cholesterol levels.

Dietary Fat Saturation and Chain Length Modulate Guinea Pig Hepatic Cholesterol Metabolism

AbstractThe effects of dietary fat saturation and saturated fatty acid composition on plasma lipoprotein concentrations and hepatic cholesterol metabolism were investigated in guinea pigs. Animals were fed semipurified diets containing 15 g fat/100 g diet, as palm kernel, palm oil, beef tallow, lard, olive oil or corn oil. Plasma lipoprotein concentrations were significantly altered by the type of dietary fat. The LDL cholesterol concentration was highest in animals fed the diet with palm kernel and lowest in animals fed the diet with corn oil, whereas HDL cholesterol was lowest in beef tallow-fed guinea pigs (P < 0.01). Hepatic cholesteryl ester concentrations were 100% higher in animals fed diets containing polyunsaturated corn oil and monounsaturated olive oil compared with animals fed any of the saturated fat diets (P < 0.01). Hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity varied in the different dietary fat groups independent of hepatic cholesterol pools or plasma LDL concentrations. In contrast, hepatic acyl-CoA: cholesterol acyltransferase (ACAT) activity was significantly correlated with plasma LDL cholesterol across all dietary groups (r = 0.63, P < 0.001). These data demonstrate that regulation of hepatic HMG-CoA reductase activity is relatively independent of changes in plasma lipoprotein levels, whereas hepatic ACAT activity exhibits a positive correlation with plasma LDL cholesterol concentrations.

Dietary fat saturation modifies the metabolism of LDL subfractions in guinea pigs.

The effects of dietary fat saturation on the metabolism of low-density lipoprotein (LDL) subfractions were measured in adult male guinea pigs fed semipurified diets containing 15% (wt/wt) corn oil (CO; 58% linoleic acid), lard (24% palmitic/14% stearic acid), or palm kernel oil (PK; 52% lauric/18% myristic acid). Animals fed the CO diet had lower plasma total cholesterol levels than guinea pigs fed the PK or lard diets (P < .01). Plasma LDL-1 (d = 1.019 to 1.05 g/mL) concentrations were 3.5- and 2.4-fold higher in animals fed the PK diet compared with the CO and lard groups, respectively, while LDL-2 (d = 1.05 to 1.09 g/mL) concentrations were not different among groups. For all dietary fat groups LDL-1 had a higher molecular weight and a larger diameter than LDL-2. LDL fractional catabolic rates (FCRs) varied, depending on both the diet and the LDL subfraction. Animals fed the polyunsaturated CO diet had a more rapid LDL FCR than animals from the other two groups (P < .01). Within the same diet group, LDL-2 exhibited a slower turnover rate than LDL-1 in animals fed the PK diet, while no differences in LDL subfraction FCR were found in the CO and lard groups. Animals fed the PK and lard diets did not exhibit significant modifications in the density distribution of LDL subfractions over a period of 33 hours. In contrast, animals fed the CO diet exhibited a shift of more buoyant to denser LDL particles, suggesting that differences in LDL intravascular processing are mediated by dietary fat saturation. In vitro LDL binding to hepatic membranes confirmed the in vivo data with an increased expression of apolipoprotein B/E receptors (Bmax) in animals fed the CO diet (P < .01). Hepatic apolipoprotein B/E receptors exhibited less affinity for LDL-2 in the PK group, a result consistent with the less rapid turnover of LDL-2 in PK-fed animals. The results suggest that dietary fatty acids varying in saturation and composition have distinctive atherogenic potentials. The lowest plasma LDL cholesterol concentrations mediated by CO intake could in part be explained by induced changes in the composition and processing of LDL subfractions, resulting in faster LDL turnover rates in addition to increased expression of hepatic apolipoprotein B/E receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Dietary impact on biliary lipids and gallstones.

Although dietary factors influence bile lithogenicity and gallstone formation, the main dietary effect appears to be indirect, depending on an interaction between caloric consumption and gender-specific aspects of lipoprotein metabolism. Excessive energy intake elicits its detrimental effect by altering lipoprotein and hepatic cholesterol metabolism in association with hyperinsulinemia. Factors, dietary and genetic, that favor elevated hepatic cholesterol synthesis and production of a bile acid profile in which chenodeoxycholic acid predominates appear to be associated with lithogenic bile. An inconsistent effect of dietary fat saturation on gallstones is that polyunsaturates possibly increase risk in men and decrease risk in women. Vegetable protein may reduce the risk of cholelithiasis. Whereas both the amount and type of dietary fiber influence cholesterol and bile lipid metabolism, specific associations between fiber and gallstones in humans remain elusive.