Abnormal fatty acid distribution of the serum phospholipids of patients with non-Hodgkin lymphoma

The data about the fatty acid (FA) status of non-Hodgkin lymphoma (NHL) patients are poor. Therefore, the aim of this study was to investigate the FA profile of serum phospholipids in NHL patients related to the aggressiveness and clinical stage of NHL. We analyzed the FA profile of serum phospholipids in 47 newly diagnosed, untreated NHL patients and in 29 healthy subjects. Significantly higher (p?<?0.001) levels of palmitic (16:0), oleic (18:1 n-9) and arachidonic acids (20:4 n-6), saturated and monounsaturated FA were found in NHL patients, while linoleic acid (18:2 n-6) and the levels of total polyunsaturated FA (PUFA), n-3 PUFA, eicosapentaenoic (20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) were significantly reduced (p?<?0.01). The level of oleic acid in patients with indolent NHL was significantly lower (p?<?0.05) than in more aggressive types of disease. Contents of palmitoleic acid, docosatetraenoic (22:4 n-6), and PUFA was lower in very aggressive NHL. According to clinical stage (CS), patients with CS I had significantly higher SFA and lower n-6 FA than other three groups, and group with CS IV showed significantly decreased DHA and n-3 PUFA. Our results showed an abnormal FA profile in serum phospholipids in NHL patients.     

Site dependency of fatty acid composition in adipose triacylglycerol in rats and its absence as a result of high-fat feeding

It is currently believed that metabolic syndrome, in general, and type 2 diabetes mellitus, in particular, depend more on visceral than on subcutaneous adipose tissue. However, the relationship between insulin resistance and fatty acid composition in visceral and subcutaneous adipose tissues remains to be clarified. In the present study, we extracted the triacylglycerol from visceral (epididymis and mesentery) and subcutaneous adipose tissues in normal and insulin-resistant, high-fat-fed (HFF) rats and determined the composition of each fatty acid. The concentrations of palmitoleic, docosapentaenoic, docosahexaenoic, dihomo-γ-linolenic, arachidonic, and docosatetraenoic acids were higher in epididymal adipose tissue than in mesenteric and subcutaneous adipose tissues; but no significant differences were detected between mesenteric and subcutaneous tissues in the normal group or among all the sites in the HFF rats. In the HFF group, stearic and oleic acid concentrations were higher, whereas n-3 and n-6 polyunsaturated ones were lower, than those in the normal group. Palmitoleic acid and some n-3 and n-6 polyunsaturated fatty acid compositions in adipose tissue triacylglycerol depend on anatomical location, which may affect the properties and/or function of adipose tissues. These results at least in part suggest that the properties of adipose tissue are difficult to distinguish based only on their "visceral" or "subcutaneous" sites. In addition, the absence of site dependence and/or difference in balance among saturated, monounsaturated, and polyunsaturated fatty acids may play an important role in the development of insulin resistance in the HFF rats.     

The effect of a menhaden oil-containing diet on hemostatic and lipid parameters of nonhuman primates with atherosclerosis

Three species of nonhuman primates were fed an atherogenic diet for 6 months (baseline period) and a menhaden oil (EPA)-containing diet for 8 weeks (test period) during which various hemostatic and lipid parameters were compared. The EPA-rich diet prolonged bleeding times, inhibited platelet aggregation response to ADP and collagen, and increased mean platelet lifespan. This diet elicited an increase in the polyunsaturated fatty acids C20:5 (EPA) and C22:6 (docosahexaenoic acid) at the expense of C18:2 (linoleic acid) and C20:4 (arachidonic acid) in pooled samples of platelet membranes, creating an increase in the ratio of n-3/n-6 polyunsaturated fatty acids. The serum lipid response to a menhaden oil diet comprised a nonsignificant decrease in total serum cholesterol and a significant decrease in HDL cholesterol.     

Contrasting effects of low or high copper intake on rat tissue lipid essential fatty acid composition

The effects of low copper intake or copper supplementation on the metabolism of stearic acid have been studied previously, but their effects on essential fatty acids have not been reported. Male Sprague-Dawley rats were fed for 12 weeks on pelleted semi-synthetic diets containing less than 1 mg/kg copper (low copper), 6 mg/kg (copper control), or 250 mg/kg copper (copper supplemented). The fatty acid composition of the total phopholipids and triglycerides of plasma, liver, heart and adipose tissue was analyzed by gas liquid chromatography. In low copper rats compared to controls, palmitic and oleic acids were decreased but stearic acid and docosahexaenoic acid were increased in plasma, liver and heart phopholipids. Arachidonic acid was also increased in plasma and liver phospholipids in low copper rats. In liver triglycerides, linoleic and arachidonic acids were increased but palmitic and oleic acid were decreased in low copper rats. Copper supplementation had the opposite effect; palmitic and oleic acids were increased in phospholipids and triglycerides whereas essential fatty acids were generally decreased. Hence, copper not only has a direct effect on the desaturation of stearic acid but also has significant effects on the tissue lipid composition of essential fatty acids.     

Diets rich in saturated n-9 and n-3 fatty acids differentially affect the fatty acid composition of phospholipids and function of rat platelets

The aim of the present study was to determine whether dietary intake of monounsaturated or long chain n-3 fatty acids could be effective in lowering platelet responsiveness through modulation of platelet phospholipid composition. Rats were fed diets containing 20% fat with equal cholesterol and 13a-tocopherol contents. These diets were supplemented with saturated, oleic or n-3 fatty acids, n-3 polyunsaturated fatty acids being added either pure, as eicosapentaenoic and docosahexaenoic ethyl esters, or as MaxEPA oil. Dietary n-3 fatty acids did not affect the oxidation status of plasma lipids. Oleic acid- and saturated fatty acid-rich diets led to similar enrichment of platelet phospholipids in arachidonic acid and to comparable thromboxane A(2) generation on stimulation with collagen or thrombin. Platelets of n-3-fed groups were differently enriched in eicosapentaenoic and docosahexaenoic acids at the expense of arachidonic acid. These groups displayed similar thromboxane A(2) production, although levels were lower than those for groups fed with oleic- or saturated fatty acid-rich diets. Only the MaxEPA diet led to a reduction in platelet reactivity, measurable as a small decrease in the aggregation induced by collagen. This diet was also responsible for a high cholesteroUphospholipid ratio and low a-tocopherol content in platelets. Overall results indicated that (i) only MaxEPA reduced platelet reactivity and (ii) this effect was moderate and apparently unrelated to platelet arachidonic acid content, membrane cholesterol to phospholipid ratio or thromboxane A(2) production.     

Diets rich in saturated n-9 and n-3 fatty acids differentially affect the fatty acid composition of phospholipids and function of rat platelets

The aim of the present study was to determine whether dietary intake of monounsaturated or long chain n-3 fatty acids could be effective in lowering platelet responsiveness through modulation of platelet phospholipid composition. Rats were fed diets containing 20% fat with equal cholesterol and 13a-tocopherol contents. These diets were supplemented with saturated, oleic or n-3 fatty acids, n-3 polyunsaturated fatty acids being added either pure, as eicosapentaenoic and docosahexaenoic ethyl esters, or as MaxEPA oil. Dietary n-3 fatty acids did not affect the oxidation status of plasma lipids. Oleic acid- and saturated fatty acid-rich diets led to similar enrichment of platelet phospholipids in arachidonic acid and to comparable thromboxane A₂ generation on stimulation with collagen or thrombin. Platelets of n-3-fed groups were differently enriched in eicosapentaenoic and docosahexaenoic acids at the expense of arachidonic acid. These groups displayed similar thromboxane A₂ production, although levels were lower than those for groups fed with oleic- or saturated fatty acid-rich diets. Only the MaxEPA diet led to a reduction in platelet reactivity, measurable as a small decrease in the aggregation induced by collagen. This diet was also responsible for a high cholesteroUphospholipid ratio and low a-tocopherol content in platelets. Overall results indicated that (i) only MaxEPA reduced platelet reactivity and (ii) this effect was moderate and apparently unrelated to platelet arachidonic acid content, membrane cholesterol to phospholipid ratio or thromboxane A₂ production.     

Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring

Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.     

Nutritional assessment and hepatic fatty acid composition in non-alcoholic fatty liver disease (NAFLD): a cross-sectional study

BACKGROUND/AIMS: Low hepatic n-6 and n-3 polyunsaturated fatty acid (PUFA) may contribute to steatosis and steatohepatitis and can be affected by diet and oxidative stress. METHODS: Seventy-three patients referred for elevated liver enzymes and suspected NAFLD were assessed. Nutritional assessment, hepatic FA composition and oxidative stress were compared between these groups: simple steatosis (SS, n=18), steatohepatitis (NASH, n=38) and minimal findings on liver biopsy (MF, n=17). RESULTS: Patients with NASH had higher: BMI, central obesity, body fat, insulin resistance, dyslipidemia and lower physical activity compared to the other groups. They also had relatively lower hepatic n-3 and n-6 PUFA, a decrease in the ratio of metabolites to essential FA precursors for both n-6 and n-3 FA (eicosapentaenoic+docosahexaenoic/linolenic and arachidonic/linoleic acid ratios) and higher liver lipid peroxides with lower antioxidant power, when compared to MF. Overall, there was no significant difference between SS and NASH in FA composition. Self-reported dietary intake and red blood cell FA composition were similar among the three groups. CONCLUSIONS: NASH patients have more metabolic abnormalities. This is associated with higher oxidative stress and lower n-3 and n-6 PUFA in the liver in the absence of any differences in dietary FA composition.     

Arachidonic acid and docosahexaenoic acid are increased in human colorectal cancer.

Increased arachidonic acid concentrations in experimental rodent colonic cancer have been described recently. In humans, a reduced erythrocyte stearic acid to oleic acid ratio has been reported in patients with colorectal cancer and it has been proposed that similar changes exist in the cancer tissue. The long chain fatty acids in the cancers of 15 patients with colorectal cancer were measured and compared with values in the unaffected mucosa. The values were expressed as mean (SD) mg fatty acid/g tissue and compared by analysis of variance. In the cancer tissue arachidonic acid was increased (0.703 (0.109) mg/g v 0.603 (0.127) mg/g, p less than 0.05) as was docosahexaenoic acid (0.211 (0.066) mg/g v 0.148 (0.039) mg/g, p less than 0.001). In contrast, the stearic acid to oleic acid ratio in the cancer tissue was increased rather than decreased, as previously suggested (0.36 (0.05) v 0.29 (0.7), p less than 0.01). Increased arachidonic acid and docosahexaenoic acid concentrations may be related to reduced lipid peroxidation, which is a feature of rapidly growing cells. Alternatively, the increased arachidonic acid values could be due to enhanced desaturase activity upon linoleic and linolenic acid, leading perhaps to increased formation of prostaglandins and other lipoxygenase products.     

Effect of dietary cholesterol on the release of prostacyclin from the mesenteric vascular bed in diabetic rat

Streptozotocin-induced diabetic female rats and age-matched control rats were fed a regular chow with or without the addition of 1% cholesterol in the diet. The release of 6-keto-PGF1 alpha, a prostacyclin metabolite, from the mesenteric vascular bed was significantly increased in diabetic rats. The production of PGI2 in diabetic rats was significantly reduced whereas that in the control was not affected by cholesterol feeding. The examination of the fatty acid composition of phospholipids from the mesenteric vascular bed indicated that proportions of stearic (18:0), linoleic (18:2n-6) and dihomo-gamma-linolenic (20:3n-6) acids were higher whereas those of oleic (18:1n-9) was lower in diabetic rats than those in the controls. Cholesterol feeding had no significant effect on the levels of arachidonic acid (20:4n-6) in the controls but it significantly decreased those in diabetic rats. It is suggested that cholesterol feeding lowers the release of PGI2 from the mesenteric vascular bed possibly because of a reduced level of arachidonic acid, the major precursor for prostaglandin synthesis. This could be due to an impairment of delta-5 desaturase.     

Hepatic and very low-density lipoprotein fatty acids in obese offspring of overfed dams

The combined effects of developmental programming and high-fat feeding at weaning on fatty acid metabolism of the offspring are not well known. In the present study, we aim at characterizing the influence of maternal and offspring's own diets on liver and very low-density lipoprotein (VLDL) lipids; fatty acid profiles of VLDL and liver phospholipids, triglycerides, and cholesteryl esters; and hepatic enzyme activities. Twenty obese male rats born to cafeteria diet–fed dams and 20 control rats born to control diet–fed dams were selected. At weaning, 10 rats of each group were fed control or cafeteria diet. Obese rats had a significant increase in serum glucose, insulin, leptin, VLDL apolipoprotein B100 and lipid levels, and hepatic fatty acid synthase and a reduction in acyl–coenzyme A oxidase and dehydrogenase activities compared with control pups at day 21 and day 90. Hepatic steatosis was apparent only at day 90. The proportions of saturated fatty acids and monounsaturated fatty acids and the oleic to stearic acid ratio were significantly increased, whereas polyunsaturated fatty acids and the arachidonic to linoleic acid ratio were decreased, in liver and VLDL lipids of obese pups compared with controls. The cafeteria diet at weaning induced more severe abnormalities in obese rats. In conclusion, maternal cafeteria diet induced a permanent reduction in hepatic β-oxidation and an increase in hepatic lipogenesis that caused liver steatosis and VLDL and fatty acid alterations in adult offspring. These preexisting alterations in offspring were worsened under a high-fat diet from weaning to adulthood. Nutritional recommendations in obesity must then target maternal and postnatal nutrition, especially fatty acid composition.     

Altered levels of n-6/n-3 fatty acids in rat heart and storage fat following variable dietary intake of linoleic acid

Fat-supplemented dies enriched with linoleic acid by the addition of 12% w/w sunflower seed oil or proportionally reduced in linoleic acid by addition of 12% mutton fat were fed to rats for 18 months before the fatty acid composition of perirenal storage fat and myocardial membranes (phospholipids) was determined. Although the fatty acid composition of perirenal fat generally reflected that of the diet, there was an inverse relationship between the consumption of n-6 and the deposition of n-9 fatty acids. In addition, enhanced deposition of oleic acid (18:1, n-9) appears to be related to the dietary intake of stearic acid (18:0). In contrast, in myocardial membranes the n-3 polyunsaturated fatty acids are found to be increased when the intake of n-6 polyunsaturated fatty acids is reduced. This is particularly evident for docosahexaenoic acid (22:6, n-3) which is significantly increased in phosphatidylcholine, phosphatidylethanolamine, and diphosphatidylglycerol fractions of myocardial membranes, when the mutton fat diet was fed. After feeding the sunflower seed oil diet, the increased consumption of linoleic acid produced only small changes in the 18:2, n-6 content of cardiac phosphatidylcholine and phosphatidylethanolamine. These major classes of membrane phospholipids also showed only small increases in 20:4, n-6. In diphosphatidylglycerol, increased 18:2, n-6 also followed increased dietary intake, but this was not accompanied by increased 20:4, n-6. These changes in myocardial phospholipid fatty acid composition are similar to those observed after short-term feeding reported previously and confirm that changes in dietary n-6/n-3 fatty acid intake affect the fatty acid composition of both myocardial membranes and storage fat. These changes persist for the duration of the feeding period.     

A new piece in the puzzling effect of n-3 fatty acids on atherosclerosis?

Omega-3 fatty acids (n-3) FA are reported to be protective against cardiovascular disease (CVD), notably through their beneficial action on atherosclerosis development. In this context dietary intake of long-chain marine eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is recommended and randomised trials largely support that EPA and DHA intake is associated with a reduction of CVD. However, mechanisms governing the atheroprotective action of n-3 FA are still unclear and numerous studies using mouse models conducted so far do not allow to reach a precise view of the cellular and molecular effects of n-3 FA on atherosclerosis. In the current issue of Atherosclerosis, Chang et al. provide important new information on the anti-atherogenic properties of n-3 FA by analysing the incremental replacement of saturated FA by pure fish oil as a source of EPA and DHA in Ldlr^−/− mice fed a high fat/high cholesterol diet.     

Fatty acid profile of erythrocyte membranes as possible biomarker of longevity

Offspring of long-lived individuals are a useful model to discover biomarkers of longevity. The lipid composition of erythrocyte membranes from 41 nonagenarian offspring was compared with 30 matched controls. Genetic loci were also tested in 280 centenarians and 280 controls to verify a potential genetic predisposition in determining unique lipid profile. Gas chromatography was employed to determine fatty acid composition, and genotyping was performed using Taqman assays. Outcomes were measured for erythrocyte membrane percentage content of saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids (omega-6 and omega-3), geometrical isomers of arachidonic and oleic acids, and total trans-fatty acids. Also, allele and genotyping frequencies at endothelial-nitric oxide synthase and delta-5/delta-6 and delta-9 desaturase loci were considered. Erythrocyte membranes from nonagenarian offspring had significantly higher content of C16:1 n-7, trans C18:1 n-9, and total trans-fatty acids, and reduced content of C18:2 n-6 and C20:4 n-6. No association was detected at endothelial-nitric oxide synthase and delta-5/delta-6 and delta-9 desaturase loci that could justify genetic predisposition for the increased trans C18:1 n-9, monounsaturated fatty acids and decreased omega-6 synthesis. We concluded that erythrocyte membranes derived from nonagenarian offspring have a different lipid composition (reduced lipid peroxidation and increased membrane integrity) to that of the general population.     

Non-alcoholic fatty liver disease in HIV infection associated with altered hepatic fatty acid composition

Hepatic fatty acid (FA) composition, especially a reduction in n-3 polyunsaturated FA (PUFA) may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is common in HIV-infection.. In a cross-sectional study we compared hepatic FA composition between 20 HIV-infected men with NAFLD (HIV/NAFLD), 21 HIV-negative men with NAFLD (NAFLD), and 7 healthy controls. Within HIV/NAFLD we compared simple steatosis (HIV/SS) to steatohepatitis (HIV/NASH). FA composition in liver and erythrocytes, oxidative stress, diet, and exercise were assessed. Major findings (P<0.05) were: 1) higher hepatic n-6/n-3 ratio in HIV/NAFLD [median (range)] [8.08 (1.08-21.52)] compared to controls [5.83 (3.58-6.93)] and NAFLD [5.97 (1.46-10.40)], with higher n-6 PUFA in HIV/NAFLD compared to NAFLD; 2) lower n-3 PUFA in erythrocytes (mol%), a marker for dietary intake, in HIV/NAFLD [5.26 (1.04-11.75)] compared to controls [8.92 (4.79-12.67)]; 3) the ratios of long-chain PUFA products to essential FA precursors of the n-6 and n-3 series were lower in HIV/NAFLD and NAFLD compared to controls. In contrast, the ratio of oleic/stearic acid was higher in HIV/NAFLD compared to the other groups. These ratios are indirect markers of enzymatic FA desaturation and elongation. Hepatic PUFA, especially biologically active long-chain PUFA, were also lower in HIV/NASH compared to HIV/SS. Oxidative stress was not different among the groups. We conclude that HIV/NAFLD is associated with altered hepatic FA composition. Changes may be due to impaired FA metabolism or suboptimal n-3 PUFA intake. The potential role of n-3 PUFA (e.g. fish oil) to treat or prevent HIV/NAFLD warrants further investigation.     

Maternal supplementation of omega 3 fatty acids to micronutrient-imbalanced diet improves lactation in rat

The present study aims to examine the effect of maternal supplementation of omega 3 fatty acids to a micronutrient (folic acid and vitamin B₁₂)-imbalanced diet on gastric milk volume and long-chain polyunsaturated fatty acid composition. Pregnant female rats were divided into 6 groups at 2 levels of folic acid in both the presence and absence of vitamin B₁₂. Both vitamin B₁₂-deficient groups were supplemented with omega 3 fatty acid. Gastric milk volume and long-chain polyunsaturated fatty acids were analyzed. Our results for the first time indicate that imbalance in maternal micronutrients reduces gastric milk volume and milk docosahexaenoic acid levels (P < .01 for both) as compared with control. Supplementation with omega 3 fatty acids to this diet imbalanced in micronutrients increases (P < .01) milk docosahexaenoic acid level as compared with control. Imbalance in maternal micronutrients during pregnancy can alter milk fatty acid composition, which may ultimately affect infant growth and development.     

Comparative changes in the fatty-acid composition of rat cardiac phospholipids after long-term feeding of sunflower seed oil- or tuna fish oil-supplemented diets

The fatty-acid composition of rat heart phospholipids was examined after long-term, i.e. more than 12 months, feeding of diets supplemented with n-6 fatty acids as sunflower seed oil (SSO), or n-3 fatty acids as tuna fish oil (TFO) which is a particularly rich source of docosahexenoic acid (DHA). Although some small changes occurred in the relative proportions of palmitic and stearic acids and in the ratio of total saturates to total unsaturates, the most important changes were in the relative proportions of 18:2 n-6 and 20:4 n-6 to 20:5 n-3 and 22:6 n-3. In general, the n-6/n-3 ratio of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and diphosphatidyl glycerol (DPG) was altered in favour of the family of fatty acids administered, although the proportions of the individual long-chain polyunsaturated fatty acids which contributed to this ratio varied from one class of phospholipids to another. In cardiac PC and PE, feeding TFO supplements reduced the proportions of arachidonic acid (AA) and significantly elevated (p less than 0.01) the proportions of DHA but produced relatively little change in those of eicosapentenoic acid (EPA). In DPG, feeding TFO led to a significant increase in the proportion of AA as well as an increase in DHA. The level of EPA was relatively low in PC, PE and DPG even after TFO feeding and never reached comparable levels with that of either AA or DHA. Nevertheless the n-6/n-3 ratio in all these classes of major cardiac phospholipids was significantly reduced by feeding TFO compared to the SSO diet or the commercial rat chow (CC) reference group. In contrast to the reports of other workers who have studied the fatty-acid composition of platelet membranes after feeding various fish oil supplements, in the rat heart the major effect of tuna fish oil is an increase in the proportion of DHA rather than EPA in the cardiac phospholipids.     

Metabolic effects of dietary stearic acid in mice: changes in the fatty acid composition of triglycerides and phospholipids in various tissues.

The fatty acid patterns of triglycerides and phospholipids extracted from adipose tissue, liver, heart, kidney, spleen, and lung of 3 groups of C57BL/6 mice were determined after feeding diets rich in palmitic acid (16:0) (high palmitic: 16:0 = 45.1% of total fatty acids), stearic acid (18:0) (high stearic: 18:0 = 42.9% of total fatty acids) and oleic acid (18:1) (high oleic: 18:1 = 79.7% of total fatty acids) for 9 months. Triglyceride content of adipose, liver, heart, kidney, lung and spleen tissues was significantly enriched in palmitic acid in mice fed the high palmitic diet (range among all tissues: 19.9% +/- 0.2% to 29.0% +/- 1.9% of total fatty acids) and in oleic acid in mice fed the high oleic diet (range 56.0% +/- 1.9% to 71.6% +/- 1.2%). The stearic acid content of organ triglycerides in mice fed the high stearic diet ranged from 3.7% +/- 0.3% to 10.8% +/- 1.2%; however, the content of oleic acid on this diet (range: 57.0% +/- 1.8% to 71.4% +/- 1.7%) was similar to the one observed in mice fed the high oleic diet. In all organs, phospholipids had a significantly higher percentage of stearic acid (range: 23.5% +/- 0.9% to 51.5% +/- 6.6%) than triglycerides, regardless of diet. To evaluate the production of oleate from stearate and palmitate, 2 groups of mice were fed the high palmitic and the high stearic diets for 1 week and then injected intravenously with [1-14C]palmitate and [1-14C]stearate and the amount of labelled oleate in liver triglycerides was measured.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unsaturated fatty acids and their oxidation products stimulate CD36 gene expression in human macrophages

Fatty acids (FA) have been implicated in the control of expression of several atherosclerosis-related genes. Similarly, the CD36 receptor has recently been shown to play an important role in atherosclerosis and other pathologies. The aim of the present study was to evaluate the direct effect of FA and their oxidation products (aldehydes), on the expression of CD36 in both THP-1 macrophages and human monocyte-derived macrophages (HMDM). The FA tested included the saturated FA (SFA) lauric, myristic, palmitic and stearic acid; the monounsaturated FA oleic acid; and the unsaturated FA (UFA) linoleic, arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Aldehydes used were malondialdehyde (MDA), hexanal, 2,4-decadienal (DDE) and 4-hydroxynonenal (HNE). CD36 expression was measured by RT-PCR, Western blot and immunofluorescence. Incubation of THP-1 macrophages for 24 h with non-cytotoxic concentrations of UFA significantly increased CD36 mRNA expression. By contrast, exposure of THP-1 macrophages to SFA did not affect the levels of CD36 mRNA. Among all UFAs tested, EPA and DHA were the strongest inducers of CD36 mRNA levels, followed by oleic and linoleic acid. Incubation of HMDM with either oleic or linoleic acid significantly increased steady-state CD36 mRNA in a dose-dependent manner. Consistent with the increase of CD36 mRNA expression, incubation of THP-1 macrophages with oleic and linoleic acid for 24 h markedly increased CD36 protein expression. Treatment of THP-1 macrophages with MDA or hexanal for 24 h significantly increased CD36 mRNA expression in a dose dependent manner. In contrast, DDE and HNE significantly decreased this parameter. The data provide evidence for a direct regulatory effect of UFA on CD36 gene expression and support a role for aldehydes in the regulation of CD36 expression by FA.     

Effects of saturated and unsaturated fatty acids on estimated desaturase activities during a controlled dietary intervention

Background and aimsDirect measurement of desaturase activities are difficult to obtain in humans. Consequently, surrogate measures of desaturase activity (estimated desaturase activities) have been frequently used in observational studies, and estimated Δ⁹- (or stearoyl-CoA-desaturase (SCD)), Δ⁶- and Δ⁵-desaturase activities have been associated with cardiometabolic disease. Data on how the markers of desaturase activities are modified by changes in dietary fat quality are lacking and therefore warrant examination.Methods and resultsIn a two-period (three weeks) strictly controlled cross-over study, 20 subjects (six women and 14 men) consumed a diet high in saturated fat (SAT-diet) and a rapeseed oil diet (RO-diet), rich in oleic acid (OA), linoleic acid (LA) and α-linolenic acid (ALA). Estimated desaturase activities were calculated as precursor to product FA ratios in serum cholesteryl esters and phospholipids. The estimated SCD [16:1 n-7/16:0] and Δ⁶-desaturase [20:3 n-6/18:2 n-6] was significantly higher while Δ⁵-desaturase [20:4 n-6/20:3 n-6] was significantly lower in the SAT-diet (P < 0.001 for all), compared to the RO-diet. The serum proportions of palmitic, stearic, palmitoleic and dihomo-γ-linolenic acids were significantly higher in the SAT-diet while the proportions of LA and ALA were significantly higher in the RO-diet.ConclusionThis is the first study to demonstrate that surrogate measures of desaturase activities change as a consequence of an alteration in dietary fat quality. Both the [16:1/16:0]-ratio and 16:1 seem to reflect changes in saturated fat intake and may be useful markers of saturated fat intake in Western countries.