Intraperitoneal Administration of Short-Chain Fatty Acids Improves Lipid Metabolism of Long-Evans Rats in a Sex-Specific Manner.

Short-chain fatty acids (SCFAs) are microbial metabolites, mainly generated by the action of gut microbiota on dietary fibers. Acetate, propionate, and butyrate are the three main SCFAs produced typically in a 60:20:20 molar ratio in the colon. Acetate, propionate, and butyrate, when given individually as supplements, have shown a protective role in obesity and hyperglycemia; however, the sex-specific effects of a mixture of SCFAs, when given in 60:20:20 ratio, on the regulation of lipid metabolism and lipid profile are not known. Male and female Long-Evans rats were given a mixture of SCFAs (acetate, propionate, and butyrate; molar ratio 60:20:20) each day for seven days intraperitoneally; plasma and hepatic lipids, gene expression, and lipidomics profile were analyzed. SCFAs significantly decreased plasma and hepatic triglycerides and cholesterol in males, whereas the fatty acyl composition of cholesteryl esters, triglycerides, and phospholipids was modulated in females. SCFAs decreased the mRNA expression of hepatic acetyl-CoA carboxylase-1 in both males and females. Our findings demonstrate for the first time that SCFAs (60:20:20) improved plasma and hepatic lipid levels and fatty acyl composition in a manner that may provide cardio-protective and anti-inflammatory effects in both sexes, via independent mechanisms.

Plasma Lipidomics Reveals Insights into Anti-Obesity Effect of Chrysanthemum morifolium Ramat Leaves and Its Constituent Luteolin in High-Fat Diet-Induced Dyslipidemic Mice.

The Chrysanthemum morifolium Ramat (CM) is widely used as a traditional medicine and herbal tea by the Asian population for its health benefits related to obesity. However, compared to the flowers of CM, detailed mechanisms underlying the beneficial effects of its leaves on obesity and dyslipidemia have not yet been elucidated. Therefore, to investigate the lipidomic biomarkers responsible for the pharmacological effects of CM leaf extract (CLE) in plasma of mice fed a high-fat diet (HFD), the plasma of mice fed a normal diet (ND), HFD, HFD plus CLE 1.5% diet, and HFD plus luteolin 0.003% diet (LU) for 16 weeks were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with multivariate analysis. In our analysis, the ND, HFD, CLE, and LU groups were clearly differentiated by partial least-squares discriminant analysis (PLS-DA) score plots. The major metabolites contributing to this differentiation were cholesteryl esters (CEs), lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), ceramides (CERs), and sphingomyelins (SMs). The levels of plasma CEs, LPCs, PCs, SMs, and CERs were significantly increased in the HFD group compared to those in the ND group, and levels of these lipids recovered to normal after administration of CLE or LU. Furthermore, changes in hepatic mRNA expression levels involved in the Kennedy pathway and sphingolipid biosynthesis were also suppressed by treatment with CLE or LU. In conclusion, this study examined the beneficial effects of CLE and LU on obesity and dyslipidemia, which were demonstrated as reduced synthesis of lipotoxic intermediates. These results may provide valuable insights towards evaluating the therapeutic effects of CLE and LU and understanding obesity-related diseases.

Hyperalphalipoproteinemic scavenger receptor BI knockout mice exhibit a disrupted epidermal lipid barrier.

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters (CE) from high-density lipoproteins (HDL). An impaired SR-BI function leads to hyperalphalipoproteinemia with elevated levels of cholesterol transported in the HDL fraction. Accumulation of cholesterol in apolipoprotein B (apoB)-containing lipoproteins has been shown to alter skin lipid composition and barrier function in mice. To investigate whether these hypercholesterolemic effects on the skin also occur in hyperalphalipoproteinemia, we compared skins of wild-type and SR-BI knockout (SR-BI-/-) mice. SR-BI deficiency did not affect the epidermal cholesterol content and induced only minor changes in the ceramide subclasses. The epidermal free fatty acid (FFA) pool was, however, enriched in short and unsaturated chains. Plasma CE levels strongly correlated with epidermal FFA C18:1 content. The increase in epidermal FFA coincided with downregulation of cholesterol and FFA synthesis genes, suggesting a compensatory response to increased flux of plasma cholesterol and FFAs into the skin. Importantly, the SR-BI-/- epidermal lipid barrier showed increased permeability to ethyl-paraminobenzoic acid, indicating an impairment of the barrier function. In conclusion, increased HDL-cholesterol levels in SR-BI-/- mice can alter the epidermal lipid composition and lipid barrier function similarly as observed in hypercholesterolemia due to elevated levels of apoB-containing lipoproteins.

Effect of Oat and Tartary Buckwheat - Based Food on Cholesterol - Lowering and Gut Microbiota in Hypercholesterolemic Hamsters.

The nutritional components in oat and tartary buckwheat had been assessed to have cholesterollowering effects. However, The effect of oat and tartary buckwheat based-food (OF) on cholesterol-lowering and gut microbiota in hypercholesterole hamsters was still limited studied because they are usually consumed in whole gran as well as after being processed. In this study, normal diets, high fat diet (HFD) with/without OF were fed to hamsters for 30 days respectively and growth parameters, metabolic parameters, and gut microbiota were investigated, respectively. It was found that OF significantly decreased plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-cholesterol), lowered liver TC, cholesterol ester (CE), and triglycerides (TG) concentrations, and increased fecal weight and bile acids (BA) concentrations, compared with HFD (p < 0.05). Moreover, the concentrations of acetate, propionate, butyrate and total short-chain fatty acids (SCFAs) were significantly increased in hamsters fed with OF, compared with HFD (p < 0.05). OF changed the overall structure of gut microbiota. The relative abundances of Erysipelotrichaceae, Ruminococcaceae, and Lachnospiraceae were decreased and the relative abundance of Eubacteriaceae was increased, compared with HFD. These results suggested that OF could reduce the concentrations of plasma lipid by inhibiting cholesterol absorption in liver and promoting excretions of fecal lipid and BA. And it also increased SCFAs and modulated the gut microbiota effectively to exert the hypocholesterolemic effects.

Effect of n-3 long-chain polyunsaturated fatty acids supplementation in healthy mothers on DHA and EPA profiles in maternal and umbilical blood: a randomized controlled trial.

Background The objective of the study was to compare the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dietary supplementation on their concentration in total lipids (TL) and lipid fractions of maternal and umbilical vein (UV) blood. The specific objective was to analyze the impact of EPA and DHA supplementation on pregnancy outcome and neonatal birth weight. Methods Women were randomly single-blinded (randomized controlled trial; ISRCTN36705743) allocated to the group receiving EPA and DHA supplementation (supplemented group) or the group receiving placebo-corn oil (control group) in the time period from January 1st, 2016 until March 1st, 2017. Women in the supplemented group (n=45) took 360 mg EPA and 240 mg DHA daily while controls (n=42) were given a placebo. Maternal and UV bloods were obtained at delivery. After lipid extraction, phospholipids (PL), cholesterol esters (CE), triacylglycerols (TG) and non-esterified fatty acids were separated by thin layer chromatography and analyzed by gas chromatography. Results Higher DHA concentrations in TL (37.24±21.87 mg/L), PL (13.14±8.07 mg/L) and triacylglycerols (2.24±2.21 mg/L) were recorded in mothers from the supplemented group when compared to the study group (TL 21.89±14.53 mg/L; P<0.001; PL 9.33±5.70 mg/L; P=0.013; TG 0.56±0.43 mg/L; P<0.001). Higher DHA concentrations in UV samples were found in TL (11.51±7.34 mg/L), PL (5.29±3.31 mg/L) and triacylglycerols (0.62±0.46 mg/L) from the supplemented groups compared with controls (TL 7.37±3.60 mg/L; P=0.002; PL 3.52±2.19 mg/L; P=0.005; TG 0.40±0.46 mg/L; P=0.035). The ratio of AA:DHA was lower in maternal (2.43) and UV serum (4.0) of the supplemented group than in the control group (maternal 3.85 P<0.001; UV 4.91 P<0.001). Conclusion The study demonstrated the higher ratio of AA/DHA in the control group indicating that pregnant women on the traditional Herzegovina diet need supplementation with DHA and EPA.

Lipidomic Response to Coffee Consumption.

Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. Our objective was to identify individual lipid changes in response to coffee drinking. We profiled the lipidome of fasting serum samples collected from a previously reported single blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were subject to quantitative lipidomic profiling using ion-mobility spectrometry⁻mass spectrometry. A total of 853 lipid species mapping to 14 lipid classes were included for univariate analysis. Three lysophosphatidylcholine (LPC) species including LPC (20:4), LPC (22:1) and LPC (22:2), significantly decreased after coffee intake (p < 0.05 and q < 0.05). An additional 72 species mapping to the LPC, free fatty acid, phosphatidylcholine, cholesteryl ester and triacylglycerol classes of lipids were nominally associated with coffee intake (p < 0.05 and q > 0.05); 58 of these decreased after coffee intake. In conclusion, coffee intake leads to lower levels of specific LPC species with potential impacts on glycerophospholipid metabolism more generally.

Açai (Euterpe oleracea Mart.) dietary intake affects plasma lipids, apolipoproteins, cholesteryl ester transfer to high-density lipoprotein and redox metabolism: A prospective study in women.

The açai fruit (Euterpe oleracea Martius), which is native to the Brazilian Amazon region, was shown to have high polyphenols and MUFA contents. In this study, we aimed to assess the effects of açai consumption on plasma lipids, apolipoproteins, the transfer of lipids to HDL (which is a relevant HDL function), and some biomarkers of redox metabolism. Forty healthy volunteer women aged 24 ± 3 years consumed 200 g of açai pulp/day for 4 weeks; their clinical variables and blood sample were obtained before and after this period. Açai pulp consumption did not alter anthropometric parameters, systemic arterial pressure, glucose, insulin and total, LDL and HDL cholesterol, triglycerides and apolipoprotein (apo) B, but it did increase the concentration of apo A-I. Açai consumption decreased the ROS, ox-LDL and malondialdehyde while increasing the activity of antioxidative paraoxonase 1. Overall, the total antioxidant capacity (TAC) was increased. Regarding the transfer of plasma lipids to HDL, açai consumption increased the transfer of cholesteryl esters (p = 0.0043) to HDL. Unesterified cholesterol, phospholipids and triglyceride transfers were unaffected. The increase in apo A-I and the cholesteryl ester transfer to HDL after the açai intake period suggests that an improvement in the metabolism of this lipoprotein occurred, and it is well known that HDL is protective against atherosclerosis. Another important finding was the general improvement of the anti-oxidant defences elicited by açai consumption. Our data indicate that açai has favourable actions on plasma HDL metabolism and anti-oxidant defence; therefore açai could have a beneficial overall role against atherosclerosis, and it is a consistently good candidate to consider as a functional food.

Selective enrichment of n-3 fatty acids in human plasma lipid motifs following intake of marine fish.

Plasma levels of n-3 long chain polyunsaturated fatty acids (LCPUFA) are associated with a reduction in risk of cardiovascular disease and other chronic, age-related diseases like Alzheimer's disease. In this work, we tested the hypothesis that n-3 LCPUFA fatty acids in human plasma are incorporated into selective lipid species following intake of n-3 LCPUFA rich marine fish. To test this hypothesis, we performed lipidomic analysis on plasma samples from a clinical trial in which participants consumed increasing amounts of farmed Atlantic salmon (Salmo salar). Under basal conditions, n-3 and n-6 LCPUFA were selectively incorporated into plasma phosphatidylcholine (PC) species containing saturated fatty acids (SFA) versus unsaturated fatty acids as the complementary fatty acids. LCPUFA were incorporated into selective triacylglycerol (TAG) species with complementary diacylglyceryl environments of 34:1 or 34:2 (for 20:5 and 22:5) and 36:2>36:3>36:4 and 36:1 (for 20:4 and 22:6). High n-3 LCPUFA marine fish intake resulted in selective increases of PC SFA_n-3 LCPUFA species and LCPUFA-containing TAG species. Changes in cholesteryl esters and phosphatidylethanolamines also occurred following fish intake. Our results highlight the importance of discriminating phospholipid and TAG species and dietary background when evaluating lipidomic outcomes and disease associations.

Lipid-lowering effect of bergamot polyphenolic fraction: role of pancreatic cholesterol ester hydrolase.

Bergamot polyphenolic fraction (BPF) has been shown to positively modulate several mechanisms involved in metabolic syndrome, suggesting its use in therapy. In particular, it is able to induce a significant amelioration of serum lipid profile in hyperlipemic patients at different levels. The purpose of our study was to investigate the effect of BPF on cholesterol absorption physiologically mediated by pancreatic cholesterol ester hydrolase (pCEH). An in vitro activity assay was performed to study the effect of BPF on pCEH, whereas the rate of cholesterol absorption was evaluated through in vivo studies. In particular, male, Sprague-Dawley rats (200–225 g) were fed either normal chow or chow supplemented with 0.5% cholic acid, 5.5% peanut oil, and varying amounts of cholesterol (0 to 1.5%). BPF (10 mg/Kg) was daily administrated by means of a gastric gavage to animals fed with lipid supplemented diet for 4 weeks and, at the end of the study, plasma lipids and liver cholesteryl esters were measured in all experimental groups. Our results show that BPF was able to inhibit pCEH activity and this effect was confirmed, in vivo, via detection of lymphatic cholesteryl ester in rats fed with a cholesterol-rich diet. This evidence clarifies a further mechanism responsible for the hypolipemic properties of BPF previously observed in humans, confirming its beneficial effect in the therapy of hypercholesterolemia and in the treatment of metabolic syndrome.

Dietary creatine supplementation lowers hepatic triacylglycerol by increasing lipoprotein secretion in rats fed high-fat diet.

Recent studies have shown that dietary creatine supplementation can prevent lipid accumulation in the liver. Creatine is a small molecule that plays a large role in energy metabolism, but since the enzyme creatine kinase is not present in the liver, the classical role in energy metabolism does not hold in this tissue. Fat accumulation in the liver can lead to the development of nonalcoholic fatty liver disease (NAFLD), a progressive disease that is prevalent in humans. We have previously reported that creatine can directly influence lipid metabolism in cell culture to promote lipid secretion and oxidation. Our goal in the current study was to determine whether similar mechanisms that occur in cell culture were present in vivo. We also sought to determine whether dietary creatine supplementation could be effective in reversing steatosis. Sprague-Dawley rats were fed a high-fat diet or a high-fat diet supplemented with creatine for 5 weeks. We found that rats supplemented with creatine had significantly improved rates of lipoprotein secretion and alterations in mitochondrial function that were consistent with greater oxidative capacity. We also find that introducing creatine into a high-fat diet halted hepatic lipid accumulation in rats with fatty liver. Our results support our previous report that liver cells in culture with creatine secrete and oxidize more oleic acid, demonstrating that dietary creatine can effectively change hepatic lipid metabolism by increasing lipoprotein secretion and oxidation in vivo. Our data suggest that creatine might be an effective therapy for NAFLD.

Plasma lipidomic profiles and cardiovascular events in a randomized intervention trial with the Mediterranean diet.

Background: Lipid metabolites may partially explain the inverse association between the Mediterranean diet (MedDiet) and cardiovascular disease (CVD).Objective: We evaluated the associations between 1) lipid species and the risk of CVD (myocardial infarction, stroke, or cardiovascular death); 2) a MedDiet intervention [supplemented with extra virgin olive oil (EVOO) or nuts] and 1-y changes in these molecules; and 3) 1-y changes in lipid species and subsequent CVD.Design: With the use of a case-cohort design, we profiled 202 lipid species at baseline and after 1 y of intervention in the PREDIMED (PREvención con DIeta MEDiterránea) trial in 983 participants [230 cases and a random subcohort of 790 participants (37 overlapping cases)].Results: Baseline concentrations of cholesterol esters (CEs) were inversely associated with CVD. A shorter chain length and higher saturation of some lipids were directly associated with CVD. After adjusting for multiple testing, direct associations remained significant for 20 lipids, and inverse associations remained significant for 6 lipids. When lipid species were weighted by the number of carbon atoms and double bonds, the strongest inverse association was found for CEs [HR: 0.39 (95% CI: 0.22, 0.68)] between extreme quintiles (P-trend = 0.002). Participants in the MedDiet + EVOO and MedDiet + nut groups experienced significant (P < 0.05) 1-y changes in 20 and 17 lipids, respectively, compared with the control group. Of these changes, only those in CE(20:3) in the MedDiet + nuts group remained significant after correcting for multiple testing. None of the 1-y changes was significantly associated with CVD risk after correcting for multiple comparisons.Conclusions: Although the MedDiet interventions induced some significant 1-y changes in the lipidome, they were not significantly associated with subsequent CVD risk. Lipid metabolites with a longer acyl chain and higher number of double bonds at baseline were significantly and inversely associated with the risk of CVD.

Effect of sardine proteins on hyperglycaemia, hyperlipidaemia and lecithin:cholesterol acyltransferase activity, in high-fat diet-induced type 2 diabetic rats.

Type 2 diabetes (T2D) is a major risk factor of CVD. The effects of purified sardine proteins (SP) were examined on glycaemia, insulin sensitivity and reverse cholesterol transport in T2D rats. Rats fed a high-fat diet (HFD) for 5 weeks, and injected with a low dose of streptozotocin, were used. The diabetic rats were divided into four groups, and they were fed casein (CAS) or SP combined with 30 or 5% lipids, for 4 weeks. HFD-induced hyperglycaemia, insulin resistance and hyperlipidaemia in rats fed HFD, regardless of the consumed protein. In contrast, these parameters lowered in rats fed SP combined with 5 or 30% lipids, and serum insulin values reduced in SP v. CAS. HFD significantly increased total cholesterol and TAG concentrations in the liver and serum, whereas these parameters decreased with SP, regardless of lipid intake. Faecal cholesterol excretion was higher with SP v. CAS, combined with 30 or 5% lipids. Lecithin:cholesterol acyltransferase (LCAT) activity and HDL3-phospholipids (PL) were higher in CAS-HF than in CAS, whereas HDL2-cholesteryl esters (CE) were lower. Otherwise, LCAT activity and HDL2-CE were higher in the SP group than in the CAS group, whereas HDL3-PL and HDL3-unesterified cholesterol were lower. Moreover, LCAT activity lowered in the SP-HF group than in the CAS-HF group, when HDL2-CE was higher. In conclusion, these results indicate the potential effects of SP to improve glycaemia, insulin sensitivity and reverse cholesterol transport, in T2D rats.

[FATTY ACID COMPOSITION OF PHOSPHOLIPIDS AND ESTERIFIED CHOLESTEROL OF THE BLOOD PLASMA OF RABBIT UNDER ARGININE ACUTE PANCREATITIS].

The content and fatty acid composition of phospholipids and esterified cholesterol were studied in the blood plasma of rabbits under acute arginine pancreatitis and its correction using linseed oil. It is established that the transport and anti-inflammatory functions of blood plasma deteriorates under acute arginine pancreatitis due to a decrease of the content of polyunsaturated fatty acids in phospholipids. The amount of cholesterol esterified with saturated and monounsaturated fatty acids increases in the blood plasma of rabbits. The concentration of phospholipids and esterified cholesterol is normalized and their fatty acid composition is improved in the lipid composition of the blood plasma of rabbits with acute arginine pancreatitis fed with linseed oil.

The Pattern of Fatty Acids Displaced by EPA and DHA Following 12 Months Supplementation Varies between Blood Cell and Plasma Fractions.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0-4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify important FA changes for plasma phosphatidylcholine (PC), cholesteryl ester (CE) and triglyceride (TAG) and for blood mononuclear cells (MNC), red blood cells (RBC) and platelets (PLAT). Dose-dependent increases in EPA + DHA were matched by decreases in several n-6 polyunsaturated fatty acids (PUFA) in PC, CE, RBC and PLAT, but were predominantly compensated for by oleic acid in TAG. Changes were observed for all FA classes in MNC. Consequently the n-6:n-3 PUFA ratio was reduced in a dose-dependent manner in all pools after 12 months (37%-64% of placebo in the four portions group). We conclude that the profile of the FA decreased in exchange for the increase in EPA + DHA following supplementation differs by FA pool with implications for understanding the impact of n-3 PUFA on blood lipid and blood cell biology.

Polyunsaturated Fat Intake Estimated by Circulating Biomarkers and Risk of Cardiovascular Disease and All-Cause Mortality in a Population-Based Cohort of 60-Year-Old Men and Women.

BACKGROUND: High intake of polyunsaturated fatty acids (PUFAs) may reduce the risk of cardiovascular disease (CVD) and mortality. Large, prospective studies including both sexes and circulating PUFAs as dietary biomarkers are needed. We investigated sex-specific associations of the major dietary PUFAs, eicosapentaenoic acid, docohexaenoic acid, linoleic acid, and α-linolenic acid, with incident CVD and all-cause mortality in a population-based cohort. METHODS AND RESULTS: PUFAs in serum cholesterol esters were measured at baseline in 60-year-old Swedish women (n=2193) and men (n=2039). With the use of national registers, 484 incident CVD events (294 men and 190 women) and 456 all-cause deaths (265 men and 191 women) were identified during follow-up (median, 14.5 years) in individuals without prior CVD at baseline. Associations of PUFAs with CVD and mortality were evaluated with Cox proportional hazard models. In multivariable-adjusted models, 1-SD increases in eicosapentaenoic acid and docohexaenoic acid were associated with lower risk of incident CVD among women (hazard ratio [HR], 0.79 [95% confidence interval (CI), 0.64-0.97] and 0.74 [95% CI, 0.61-0.89], respectively). α-Linolenic acid was associated with moderately increased CVD risk in women (HR, 1.16; 95% CI, 1.02-1.32). Inverse associations with all-cause mortality were observed for eicosapentaenoic acid and docohexaenoic acid among all participants (HR, 0.81 [95% CI, 0.72-0.91] and 0.80 [95% CI, 0.72-0.89], respectively) and for linoleic acid in men (HR, 0.73; 95% CI, 0.64-0.83). CONCLUSIONS: Serum linoleic acid and very-long-chain n-3 PUFAs, partly reflecting vegetable oil and fish intake, respectively, were inversely associated with all-cause mortality. Inverse associations of eicosapentaenoic acid and docohexaenoic acid with incident CVD were observed only in women.

High-oleic canola oil consumption enriches LDL particle cholesteryl oleate content and reduces LDL proteoglycan binding in humans.

Oleic acid consumption is considered cardio-protective according to studies conducted examining effects of the Mediterranean diet. However, animal models have shown that oleic acid consumption increases LDL particle cholesteryl oleate content which is associated with increased LDL-proteoglycan binding and atherosclerosis. The objective was to examine effects of varying oleic, linoleic and docosahexaenoic acid consumption on human LDL-proteoglycan binding in a non-random subset of the Canola Oil Multi-center Intervention Trial (COMIT) participants. COMIT employed a randomized, double-blind, five-period, cross-over trial design. Three of the treatment oil diets: 1) a blend of corn/safflower oil (25:75); 2) high oleic canola oil; and 3) DHA-enriched high oleic canola oil were selected for analysis of LDL-proteoglycan binding in 50 participants exhibiting good compliance. LDL particles were isolated from frozen plasma by gel filtration chromatography and LDL cholesteryl esters quantified by mass-spectrometry. LDL-proteoglycan binding was assessed using surface plasmon resonance. LDL particle cholesterol ester fatty acid composition was sensitive to the treatment fatty acid compositions, with the main fatty acids in the treatments increasing in the LDL cholesterol esters. The corn/safflower oil and high-oleic canola oil diets lowered LDL-proteoglycan binding relative to their baseline values (p = 0.0005 and p = 0.0012, respectively). At endpoint, high-oleic canola oil feeding resulted in lower LDL-proteoglycan binding than corn/safflower oil (p = 0.0243) and DHA-enriched high oleic canola oil (p = 0.0249), although high-oleic canola oil had the lowest binding at baseline (p = 0.0344). Our findings suggest that high-oleic canola oil consumption in humans increases cholesteryl oleate percentage in LDL, but in a manner not associated with a rise in LDL-proteoglycan binding.

Lipidome of atherosclerotic plaques from hypercholesterolemic rabbits.

The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework of the lipids that comprise the atherosclerotic lesion of a widely used pre-clinical model of plaque progression. Male New Zealand White rabbits were administered regular chow supplemented with 0.5% cholesterol (HC) for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our lipidomic analyses of plaques isolated from rabbits fed the HC diet, using ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry, detected most of the major lipid classes including: Cholesteryl esters, triacylglycerols, phosphatidylcholines, sphingomyelins, diacylglycerols, fatty acids, phosphatidylserines, lysophosphatidylcholines, ceramides, phosphatidylglycerols, phosphatidylinositols and phosphatidylethanolamines. Given that cholesteryl esters, triacylglycerols and phosphatidylcholines comprise greater than 75% of total plasma lipids, we directed particular attention towards the qualitative and quantitative assessment of the fatty acid composition of these lipids. We additionally found that sphingomyelins were relatively abundant lipid class within lesions, and compared the abundance of sphingomyelins to their precursor phosphatidylcholines. The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome.

Cancer death is related to high palmitoleic acid in serum and to polymorphisms in the SCD-1 gene in healthy Swedish men.

BACKGROUND: A high proportion of monounsaturated fatty acids (MUFAs) or a high ratio of MUFAs to saturated fatty acids in plasma, reflecting a high activity of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1), has been shown to be related to cancer death and incidence in some studies. OBJECTIVES: The objective was to study whether the serum cholesteryl ester proportion of palmitoleic acid [16:1n-7 (16:1ω-3)] and the ratio of palmitoleic to palmitic acid (16:1n-7/16:0), as an estimation of the activity of SCD-1, are related to cancer death and to investigate whether polymorphisms in the SCD-1 gene are related to cancer mortality. DESIGN: A community-based cohort of 50-y-old men was followed for a maximum of >40 y. Survival analysis was used to relate fatty acid composition in serum, analyzed at baseline by gas-liquid chromatography (n = 1981), and single nucleotide polymorphisms in the SCD-1 gene (n = 986) to cancer death. A 7-d dietary record was completed at age 70 y (n = 880). RESULTS: The proportions of 16:1n-7 and the ratio of 16:1n-7 to 16:0 were associated with cancer mortality during follow-up in a comparison of the highest with the lowest quartile of 16:1n-7 (adjusted HR: 1.37; 95% CI: 1.04, 1.82). Inherited variance of the SCD-1 gene seemed to be related to cancer death, especially among men with a low proportion of PUFA in the diet in a comparison of the highest with the lowest weighted genetic risk score (HR: 2.14; 95% CI: 1.13, 4.04). CONCLUSION: The findings are compatible with the hypothesis that there is an association between endogenously synthesized MUFAs and cancer death.

Dietary fat intake, circulating and membrane fatty acid composition of healthy Norwegian men and women.

BACKGROUND: The present study aimed to assess the dietary fat intake and blood fatty acid status of healthy Norwegian men and women living in Bergen whose habitual diet is known to be high in long-chain omega-3 fat. METHODS: Healthy men (n = 41) and women (n = 40) aged 20-50 years who were regular blood donors completed 7-day food diaries and their nutrient intake was analysed by Norwegian food database software, kbs, version 4.9 (kostberegningssystem; University of Oslo, Oslo, Norway). Blood samples were obtained before blood donation and assessed for the fatty acid composition of plasma triglycerides and cholesterol esters, phosphatidylcholine, and red cell phosphatidylcholine and phosphatidylethanolamine. RESULTS: There was no difference in dietary fat intake between men and women. Total and saturated fat intakes exceeded the upper limits of the recommendations of the National Nutrition Council of Norway. Although polyunsaturated fat intake was close to the lower limit of the recommended level, the intake varied greatly among individuals, partly as a result of the use of supplementary fish oil. Moreover, the proportional fatty acid composition of plasma and red cell lipids was similar between men and women. Enrichment of docosahexaenoic acid in red cell phosphatidylethanolamine was found in fish oil users. CONCLUSIONS: The results of the present study provide a snapshot of the current nutritional status of healthy Norwegian adults. Moreover, the detailed blood fatty acid composition of men and women whose habitual diet constitutes high long-chain polyunsaturated omega-3 fat as well as saturated fat could be used as reference value for population studies.