Hypercholesterolaemic effects of saturated fatty acids (SFA) may be influenced not only by the chain length, but also by their specific location within the triacylglycerol (TAG) molecule. We examined ...the hypothesis that dietary fats rich in SFA, but containing mostly unsaturated fatty acids in the sn-2 position with most SFA in sn-1 and -3 (palm olein PO and cocoa butter CB) will have similar serum lipid outcomes to unsaturated olive oil (OO).
Thirty-eight participants (20-40 yr, 18.5- ≤ 27.5 kg/m
) completed a 4-week randomised 3 × 3 crossover feeding intervention, preceded by 2-week run-in and separated by 2-week washout periods. Background diet contained 35 percentage of total energy (%E) fat, 18%E protein, 48%E carbohydrates, differing in test fats only (palm olein (PO), CB, OO; 20%E). Total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) ratio and related variables; TC, HDL-C, low density lipoprotein cholesterol (LDL-C), TAG, apoA1, ApoB, ApoA1 (apolipoprotein A1)/ApoB (apolipoprotein B), lipoprotein (a) (Lp(a)), NEFA, LDL sub-fractions, were assessed pre- and post-intervention. Data were analysed using mixed effects longitudinal models with a P-value < 0.05 considered significant.
Changes in plasma fatty acids (P < 0.05) confirmed compliance; C18:1 increased with OO compared to PO and CB; C16:0 decreased with OO and C18:0 increased following CB. No differences were seen for TC/HDL-C (mean 95%CI change for PO, 0.080.00, 0.15 mmol/L; CB, 0.06 -0.05, 0.16 mmol/L; and OO, -0.01 -0.15, 0.13 mmol/L; P = 0.53 or any other parameter including LDL sub-fractions. OO decreased IDL-A compared to PO (-2.2 -4.31, -0.21 mg/dL, P = 0.03).
In healthy young participants, plasma lipid responses to PO and CB, enriched in SFA but having primarily unsaturated fatty acid in the sn-2 position of TAG, did not differ from OO.
The central feature of NAFLD is a disturbed fatty-acid metabolism with hepatic lipid accumulation. However, the factors that determine the severity of NAFLD, including the role of nutrition, gender, ...and plasma lipid levels, remain to be determined.
High-fat diets (42 en% fat), containing 0.2% cholesterol, were fed to male and female wild-type and hyperlipidemic APOE2ki C57BL/6J mice for three weeks. The fats were, in order of decreasing saturation, fractionated palm fat (fPF; ~95%), cocoa butter (CB; ~60%), olive oil (OO; ~15%), sunflower oil (SO; ~12%), and high-oleic-acid sunflower oil (hoSO; ~7%). Plasma and liver triglycerides (concentration and composition), liver inflammation (Ccl2, Cd68, Tnf-α mRNA), and infiltration of macrophages (Cd68, Cd11b immunohistochemistry) and neutrophils (Mpo) were quantified.
Addition of cholesterol to a low-fat diet decreased plasma HDL and increased (V)LDL levels in APOE2ki mice. Plasma cholesterol levels in female, but not male APOE2ki mice correlated significantly with inflammation. Kupffer cells of inflamed livers were swollen. Wild-type mice refused the highly saturated fPF diet. The high-fat CB, OO, and SO diets induced hyperglycemia and a 2-fold increase in hepatic fat content in male, but not female wild-type mice (in females, hepatic fat content was similar to that in males fed a high-fat diet). All high-fat diets induced macrovesicular setatosis. APOE2ki mice were protected against high-fat diet-induced steatosis and hyperglycemia, except when fed a hoSO diet. This diet caused a 5-fold increase in liver triglyceride and mead-acid content, and an increased expression of lipogenic genes, suggesting a deficiency in poly-unsaturated fatty acids. Irrespective of the composition of the high-fat diet, oleic acid was the main triglyceride component of liver fat in wild-type and APOE2ki mouse livers. Liver inflammation was dependent on genotype (APOE2ki > wild type), gender (female > male), and cholesterol content (high > low) of the diet, but not on dietary fat composition.
Dietary cholesterol plays a determining, independent role in inflammation, especially in female mice. The fatty-acid saturation of the diet hardly affected hepatic steatosis or inflammation.
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