Different Serum Free Fatty Acid Profiles in NAFLD Subjects and Healthy Controls after Oral Fat Load.

BACKGROUND: Free fatty acid (FFA) metabolism can impact on metabolic conditions, such as obesity and nonalcoholic fatty liver disease (NAFLD). This work studied the increase in total FFA shown in NAFLD subjects to possibly characterize which fatty acids significantly accounted for the whole increase. METHODS: 21 patients with NAFLD were selected according to specified criteria. The control group consisted of nine healthy subjects. All subjects underwent an oral standard fat load. Triglycerides; cholesterol; FFA; glucose and insulin were measured every 2 h with the determination of fatty acid composition of FFA. RESULTS: higher serum FFA levels in NAFLD subjects are mainly due to levels of oleic, palmitic and linoleic acids at different times. Significant increases were shown for docosahexaenoic acid, linolenic acid, eicosatrienoic acid, and arachidonic acid, although this was just on one occasion. In the postprandial phase, homeostatic model assessment HOMA index positively correlated with the ω3/ω6 ratio in NAFLD patients. CONCLUSIONS: the higher serum levels of FFA in NAFLD subjects are mainly due to levels of oleic and palmitic acids which are the most abundant circulating free fatty acids. This is almost exactly corresponded with significant increases in linoleic acid. An imbalance in the n-3/n-6 fatty acids ratio could modulate postprandial responses with more pronounced effects in insulin-resistant subjects, such as NAFLD patients.

Phytosterol-enriched yogurt increases LDL affinity and reduces CD36 expression in polygenic hypercholesterolemia.

Dietary enrichment with phytosterols (plant sterols similar to cholesterol) is able to reduce plasma cholesterol levels due to reduced intestinal absorption. The aim of this study was to investigate the effect of phytosterol-enriched yogurt consumption on the major serum lipid parameters, low density lipoprotein (LDL) receptor activity, LDL-receptor affinity, and CD36 expression in hypercholesterolemic subjects. Fifteen patients affected by polygenic hypercholesterolemia were evaluated in a single-blind randomized crossover study after a 4 weeks treatment with a phytosterol-enriched yogurt containing 1.6 g esterefied phytosterols (equivalent to 1.0 g free phytosterol). Lipid parameters were compared with a phytosterol-free placebo-controlled diet. The effect of the two treatments on each variable, measured as percentage change, was compared by paired samples t test and covariance analysis. The treatment induced a modest but significant decrease in LDL-cholesterol levels (4.3%, P = 0.03) and a significant increase in high density lipoprotein (HDL) 3-cholesterol (17.1%, P = 0.01). Phytosterol consumption had no effect on LDL-receptor activity whereas patient LDL-receptor affinity significantly increased (9.7%, P = 0.01) and CD36 expression showed a marked significant decrease (18.2%, P = 0.01) in the phytosterol-enriched yoghurt patients. Our data show that the oral administration of a phytosterol-enriched yogurt has modest but significant effects on commonly measured lipid parameters. The improvement of LDL-receptor affinity and the reduction in CD36 expression may reflect an important antiatherogenic effect.

Microsomal triglyceride transfer protein 493-T variant is associated with resistin levels and C-reactive protein.

BACKGROUND: The microsomal triglyceride transfer protein (MTP) is a heterodimeric lipid transfer protein that consists of a large unique 97-kDA subunit and protein disulfide isomerase. MTP is involved in the assembly of apoB-containing lipoprotein and enables the secretion of VLDLs by the liver and chylomicrons by the intestine. The MTP gene is highly polymorphic. The less common T variant has been associated with the reduction of plasma LDL-cholesterol levels and with an increased risk in coronary heart disease. We hypothesized that MTP polymorphism could be associated to LDL-cholesterol levels and proinflammatory cytokines, such as resistin. METHODS AND RESULTS: The -493G/T MTP gene polymorphism was investigated in 290 subjects. Subjects carrying the TT genotype had lower level of LDL-cholesterol and higher serum resistin levels than individual carrying one or two copies of the -493G allele. After adjustments for age, BMI, waist circumference, alcohol intake and exercise levels, a significant direct association was evident between hs-CRP and resistin levels and the presence of the TT genotype in a multiple regression model. CONCLUSION: This study supports the notion that the rare MTP-493T/T genotype is associated both with higher levels of inflammatory parameters and with low levels of LDL-cholesterol. Prospective data are needed to investigate if the association between CVD and the MTP-493T/T genotype might be due to the increased sub-clinical proinflammatory state associated with this mutation.

RETRACTED: Postprandial lipemia and LDL conjugated dienes predict serum GGT and liver histology in NASH.

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Influence of cyclosporine on low-density lipoprotein uptake in human lymphocytes.

Low-density lipoprotein (LDL) levels are often elevated in renal transplant recipients, and cyclosporine (CsA) therapy in these patients has been implicated. Cardiovascular disease is the major cause of mortality in transplant recipients, and alterations of lipid metabolism represent a common risk factor. The role of CsA on LDL metabolism is still partially defined. The aim of the study was to evaluate the LDL receptor uptake of CsA-transported LDL (CsA-LDL) compared with normal LDL in normal and CsA-treated lymphocytes. Forty-seven healthy unrelated subjects and 6 CsA-treated patients were consecutively enrolled as donors of lymphocytes to measure receptor-mediated LDL metabolism. Normal LDL and CsA-LDL were isolated from blood donors and from patients under CsA immunosuppressive therapy, respectively. Lipoproteins were labeled with a fluorochrome, and LDL receptor uptake was measured by flow cytometry. Normal LDL uptake was 13.95% +/- 4.5%, whereas CsA-LDL uptake was 32.47% +/- 10.84% (P < .001) in healthy lymphocytes. In CsA-treated lymphocytes, normal LDL uptake was 7.48% +/- 2.32% vs 12.49% +/- 2.44% CsA-LDL (P < .01). Lymphocytes of every subject showed at least a 2-fold increased uptake of CsA-LDL vs normal LDL. Our data show that CsA-LDL is internalized more than normal LDL via the LDL receptor in both human healthy and CsA-treated lymphocytes. CsA-treated lymphocytes, in comparison to normal lymphocytes, exhibit a reduced LDL receptor activity.

Lipoprotein-apolipoprotein changes in renal transplant recipients.

Recent studies have demonstrated that the incidence of cardiovascular events occurring with renal transplantation is higher than that in the general population. Renal transplantation modifies the characteristic dyslipidemia of chronic renal failure. In this study the change in lipoprotein and lipid values of 103 transplant recipients after transplantation was investigated. The aim of our work was to examine the short-term and long-term variations in lipid metabolism. The major lipoprotein fractions (VLDL, LDL, HDL) were separated by preparative ultracentrifugation, and TG and cholesterol concentrations were determined in plasma and lipoprotein fractions. Whole plasma apolipoproteins were determined by a rate immunonephelometric technique. In the pretransplant period the patients displayed the typical picture of uremics. After transplantation the most evident alterations in the lipoprotein profile occurred in our case series after 3 mon. The major finding was a 35% reduction in plasma TG. The modifications in the TG-rich lipoproteins of our transplant recipients persisted throughout the observation period. In the initial 3-mon period, total cholesterol remained steady, whereas LDL-cholesterol and total apolipoprotein B showed a significant increase. No significant changes were found in total and transported TG and cholesterol between the 3-mon and the 6-yr values. The substantial stability of cholesterol levels after transplantation and in subsequent reports, as well as a higher incidence of cardiovascular complications, may suggest that the mechanisms responsible for vessel damage must be sought mainly in the structural and physicochemical alterations of the individual lipoprotein fractions or in other risk factors.