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Background: Accumulation of saturated fatty acids (SFAs) in the liver is known to induce hepatic steatosis and inflammation causing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Although SFAs have been shown to affect the epigenome in whole blood, pancreatic islets, and adipose tissue in humans, and genome-wide DNA methylation studies have linked epigenetic changes to NAFLD and NASH, studies focusing on the association of SFAs and DNA methylation in human liver are missing. We, therefore, investigated whether human liver SFA content associates with DNA methylation and tested if SFA-linked alterations in DNA methylation associate with NAFLD-related clinical phenotypes in obese individuals. Results: We identified DNA methylation (Infinium HumanMethylation450 BeadChip) of 3169 CpGs to be associated with liver total SFA content (q-value < 0.05) measured using proton NMR spectroscopy in participants of the Kuopio Obesity Surgery Study (n = 51; mean ± SD:49.3 ± 8.5 years old; BMI:43.7 ± 6.2 kg/m2). Of these 3169 sites, 797 overlapped with previously published NASH-associated CpGs (NASH-SFA), while 2372 CpGs were exclusively associated with SFA (Only-SFA). The corresponding annotated genes of these only-SFA CpGs were found to be enriched in pathways linked to satiety and hunger. Among the 54 genes mapping to these enriched pathways, DNA methylation of CpGs mapping to PRKCA and TSPO correlated with their own mRNA expression (HumanHT-12 Expression BeadChip). In addition, DNA methylation of another ten of these CpGs correlated with the mRNA expression of their neighboring genes (p value < 0.05). The proportion of CpGs demonstrating a correlation of DNA methylation with plasma glucose was higher in NASH-SFA and only-SFA groups, while the proportion of significant correlations with plasma insulin was higher in only-NASH and NASH-SFA groups as compared to all CpGs on the Illumina 450 K array (Illumina, San Diego, CA, USA). Conclusions: Our results suggest that one of the mechanisms how SFA could contribute to metabolic dysregulation in NAFLD is at the level of DNA methylation. We further propose that liver SFA-related DNA methylation profile may contribute more to hyperglycemia, while insulin-related methylation profile is more linked to NAFLD or NASH. Further research is needed to elucidate the molecular mechanisms behind these observations. [ABSTRACT FROM AUTHOR]

Background: Accumulation of saturated fatty acids (SFAs) in the liver is known to induce hepatic steatosis and inflammation causing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Although SFAs have been shown to affect the epigenome in whole blood, pancreatic islets, and adipose tissue in humans, and genome-wide DNA methylation studies have linked epigenetic changes to NAFLD and NASH, studies focusing on the association of SFAs and DNA methylation in human liver are missing. We, therefore, investigated whether human liver SFA content associates with DNA methylation and tested if SFA-linked alterations in DNA methylation associate with NAFLD-related clinical phenotypes in obese individuals. Results: We identified DNA methylation (Infinium HumanMethylation450 BeadChip) of 3169 CpGs to be associated with liver total SFA content (q-value < 0.05) measured using proton NMR spectroscopy in participants of the Kuopio Obesity Surgery Study (n = 51; mean ± SD:49.3 ± 8.5 years old; BMI:43.7 ± 6.2 kg/m2). Of these 3169 sites, 797 overlapped with previously published NASH-associated CpGs (NASH-SFA), while 2372 CpGs were exclusively associated with SFA (Only-SFA). The corresponding annotated genes of these only-SFA CpGs were found to be enriched in pathways linked to satiety and hunger. Among the 54 genes mapping to these enriched pathways, DNA methylation of CpGs mapping to PRKCA and TSPO correlated with their own mRNA expression (HumanHT-12 Expression BeadChip). In addition, DNA methylation of another ten of these CpGs correlated with the mRNA expression of their neighboring genes (p value < 0.05). The proportion of CpGs demonstrating a correlation of DNA methylation with plasma glucose was higher in NASH-SFA and only-SFA groups, while the proportion of significant correlations with plasma insulin was higher in only-NASH and NASH-SFA groups as compared to all CpGs on the Illumina 450 K array (Illumina, San Diego, CA, USA). Conclusions: Our results suggest that one of the mechanisms how SFA could contribute to metabolic dysregulation in NAFLD is at the level of DNA methylation. We further propose that liver SFA-related DNA methylation profile may contribute more to hyperglycemia, while insulin-related methylation profile is more linked to NAFLD or NASH. Further research is needed to elucidate the molecular mechanisms behind these observations. [ABSTRACT FROM AUTHOR]

Purpose: Fatty acid desaturase (FADS) variants associate with fatty acid (FA) and adipose tissue (AT) metabolism and inflammation. Thus, the role of FADS1 variants in the regulation of dietary linoleic acid (LA)-induced effects on AT inflammation was investigated. Methods: Subjects homozygotes for the TT and CC genotypes of the FADS1-rs174550 (TT, n = 25 and CC, n = 28) or -rs174547 (TT, n = 42 and CC, n = 28), were either recruited from the METabolic Syndrome In Men cohort to participate in an intervention with LA-enriched diet (FADSDIET) or from the Kuopio Obesity Surgery (KOBS) study. GC and LC–MS for plasma FA proportions and eicosanoid concentrations and AT gene expression for AT inflammatory score (AT-InSc) was determined. Results: We observed a diet-genotype interaction between LA-enriched diet and AT-InSc in the FADSDIET. In the KOBS study, interleukin (IL)1 beta mRNA expression in AT was increased in subjects with the TT genotype and highest LA proportion. In the FADSDIET, n-6/LA proportions correlated positively with AT-InSc in those with the TT genotype but not with the CC genotype after LA-enriched diet. Specifically, LA- and AA-derived pro-inflammatory eicosanoids related to CYP450/sEH-pathways correlated positively with AT-InSc in those with the TT genotype, whereas in those with the CC genotype, the negative correlations between pro-inflammatory eicosanoids and AT-InSc related to COX/LOX-pathways. Conclusions: LA-enriched diet increases inflammatory AT gene expression in subjects with the TT genotype, while CC genotype could play a protective role against LA-induced AT inflammation. Overall, the FADS1 variant could modify the dietary LA-induced effects on AT inflammation through the differential biosynthesis of AA-derived eicosanoids. [ABSTRACT FROM AUTHOR]

Purpose: We studied the effects of a physical activity and dietary intervention on plasma lipids in a general population of children. We also investigated how lifestyle changes contributed to the intervention effects. Methods: We carried out a 2-year controlled, non-randomized lifestyle intervention study among 504 mainly prepubertal children aged 6–9 years at baseline. We assigned 306 children to the intervention group and 198 children to the control group. We assessed plasma concentrations of total, LDL, HDL, and VLDL cholesterol, triglycerides, HDL triglycerides, and VLDL triglycerides. We evaluated the consumption of foods using 4-day food records and physical activity using a movement and heart rate sensor. We analyzed data using linear mixed-effect models adjusted for age at baseline, sex, and pubertal stage at both time points. Furthermore, specific lifestyle variables were entered in these models. Results: Plasma LDL cholesterol decreased in the intervention group but did not change in the control group (− 0.05 vs. 0.00 mmol/L, regression coefficient (β) = − 0.0385, p = 0.040 for group*time interaction). This effect was mainly explained by the changes in the consumption of high-fat vegetable oil-based spreads (β = − 0.0203, + 47% change in β) and butter-based spreads (β = − 0.0294, + 30% change in β), moderate-to-vigorous physical activity (β = − 0.0268, + 30% change in β), light physical activity (β = − 0.0274, + 29% change in β) and sedentary time (β = − 0.0270, + 30% change in β). The intervention had no effect on other plasma lipids. Conclusion: Lifestyle intervention resulted a small decrease in plasma LDL cholesterol concentration in children. The effect was explained by changes in quality and quantity of dietary fat and physical activity. Clinical Trial Registry Number: NCT01803776, ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: The health benefits of substituting dietary polyunsaturated fatty acids (PUFAs) for saturated fatty acids are well known. However, limited information exists on how the response to dietary intake of linoleic acid (LA; 18:2n–6) is modified by polymorphisms in the fatty acid desaturase (FADS) gene cluster. Objectives: The aim of the current study was to test the hypothesis that the FADS1 rs174550 genotype modifies the effect of dietary LA intake on the fatty acid composition of plasma lipids, fasting glucose, and high-sensitivity C-reactive protein (hsCRP). Methods: Associations were investigated between genotype, plasma PUFAs, fasting glucose, and hsCRP concentrations in the cross-sectional, population-based Metabolic Syndrome in Men cohort (n = 1337). In addition, 62 healthy men from the cohort who were homozygotes for the TT or CC genotype of the FADS1 rs174550 were recruited to a 4-wk intervention (FADSDIET) with an LA-enriched diet. The fatty acid composition of plasma PUFAs and concentrations of plasma fasting glucose, serum hsCRP, and plasma lipid mediators (eicosanoids and related analogs) were measured at the beginning and end of the 4-wk intervention period. Results: In the FADSDIET trial, the plasma LA proportion increased in both genotype groups in response to an LA-enriched diet. Responses in concentrations of serum hsCRP and plasma fasting glucose and the proportion of arachidonic acid (20:4n–6) in plasma phospholipids and cholesteryl esters differed between genotype groups (interaction of diet × genotype, P < 0.05). In TT homozygous subjects, plasma eicosanoid concentrations correlated with the arachidonic acid proportion in plasma and with hsCRP (r = 0.4–0.7, P < 0.05), whereas in the CC genotype there were no correlations. Conclusions: Our findings show that the FADS1 genotype modifies metabolic responses to dietary LA. The emerging concept that personalized dietary counseling should be modified by the FADS1 genotype needs to be tested in larger randomized trials [ABSTRACT FROM AUTHOR]

Objective Fatty acid (FA) composition affects obesity-associated low-grade inflammation. It has been shown that the fatty acid desaturase ( FADS) 2 gene polymorphism associates with FA metabolism and adipose tissue (AT) inflammation. This study aimed to investigate the relationship between FA metabolism and inflammation in different tissues and the possible interorgan cross talk. Methods Cross-sectional baseline data from 155 individuals with obesity (both male and female) participating in the Roux-en-Y gastric bypass operation in the ongoing Kuopio Obesity Surgery Study were used. Gas chromatograph for FA composition, liver histology, and targeted RNA expression for gene expression profile were performed. Results It was demonstrated that the saturated fatty acid (SFA) proportion in AT correlated positively with inflammation in subcutaneous AT (SAT) and visceral AT (VAT) but not in the liver, while the monounsaturated fatty acid (MUFA) proportion in SAT and VAT correlated negatively with AT inflammation. Notably, there was a positive correlation between AT n-6 polyunsaturated fatty acids (PUFAs), but not AT SFAs or MUFAs, and liver inflammation. This correlation was modified by the FADS2 genotype. Conclusions The AT FA profile relates with AT inflammation. Additionally, there seems to be a complex interaction, partly regulated by the FADS2 genotype, regulating the interaction between FAs in AT and liver inflammation. [ABSTRACT FROM AUTHOR]

Background: Evidence on the effects of lifestyle interventions on plasma fatty acid composition in children is limited. Objective: We investigated the effects of a dietary and physical activity intervention on plasma fatty acid composition of cholesteryl esters (CEs) and phospholipids and estimated desaturase and elongase activities in children. Design: We conducted a 2-y controlled dietary and physical activity intervention based on Finnish nutrition and physical activity recommendations in a population sample of 506 children aged 6-8 y. We assessed plasma fatty acid composition by gas chromatography and estimated desaturase and elongase activities as the ratio of product fatty acids to precursor fatty acids. We analyzed data by using linear mixed models adjusted for age and sex. Results: The proportion of total polyunsaturated fatty acids (PUFAs) in CEs tended to increase in the intervention group compared with the control group (P = 0.007 for group × time interaction). The proportion of total PUFAs in phospholipids (P = 0.019 for group × time interaction) and the proportion of linoleic acid in CEs (P = 0.038 for group × time interaction) decreased in the control group. The proportion of a-linolenic acid in CEs (P < 0.001 for group × time interaction) increased and in phospholipids (P = 0.015 for group × time interaction) tended to increase in the intervention group. The proportion of stearic acid in CEs decreased in the intervention group (P = 0.001 for group × time interaction). The proportion of oleic acid in CEs (P = 0.002 for group × time interaction) increased and in phospholipids (P = 0.023 for group × time interaction) tended to increase in the control group. Estimated elongase activity in CEs decreased in the control group (P = 0.050 for group × time interaction). Intervention had no effect on estimated desaturase activities. Conclusions: Dietary and physical activity intervention had a beneficial effect on plasma fatty acid composition in children by preventing the decrease in the proportion of total PUFAs and linoleic acid and by increasing the proportion of α-linolenic acid. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Our aim was to investigate the fasting proportions of fatty acids and estimated desaturase and elongase activities in three different lipid fractions in plasma, phospholipids (PLs), cholesteryl esters (CEs) and triacylglycerols (TGs), as predictors for the worsening of glycaemia (area under the glucose curve in an OGTT [glucose AUC]) and incident type 2 diabetes in a 5.9 year follow-up of the Metabolic Syndrome in Men population-based cohort. Methods: Fatty acid proportions were measured in plasma PL, CE and TG fractions in 1,364 Finnish men aged 45-68 years at baseline. The prospective follow-up study included only men who were non-diabetic at baseline and had data available at follow-up ( n = 1,302). A total of 71 participants developed new type 2 diabetes during follow-up. Results: After adjusting for confounding factors, total saturated fatty acids, palmitoleic acid (16:1 n-7), dihomo-γ-linolenic acid (20:3 n-6) and estimated stearoyl-CoA desaturase 1 and Δ-desaturase (D6D) enzyme activities significantly predicted the worsening of glycaemia whereas total polyunsaturated fatty acid, linoleic acid (18:2 n-6) and elongase activity predicted a decrease in the glucose AUC. Estimated D6D activity and dihomo-γ-linolenic acid (20:3 n-6) were associated with an increased risk of incident type 2 diabetes. Results were consistent across the three different lipid fractions. However, fatty acid proportions in the PL and CE fractions were stronger predictors for glycaemia and incident type 2 diabetes compared with fatty acid proportions in the TG fraction. Conclusions/interpretation: Selected fatty acid proportions of plasma lipid fractions and their ratios, which reflect desaturase and elongase enzyme activities, may be good biomarkers for the worsening of glycaemia and incident type 2 diabetes. [ABSTRACT FROM AUTHOR]

Human and animal studies suggest an interaction between the Pro12Ala polymorphism of PPARG and dietary fat. In this randomized crossover clinical trial, we investigated whether subjects with the Pro12Pro and Ala12Ala genotypes of PPARG respond differently to a diet supplemented with high saturated (SAFA) or polyunsaturated fatty acid (PUFA).We recruited non-diabetic men from a populationbased METSIM study (including 10,197 men) to obtain men with the Ala12Ala and the Pro12Pro genotypes matched for age and body mass index. Seventeen men with the Pro12Pro genotype and 14 with the Ala12Ala genotype were randomized to both a PUFA diet and a SAFA diet for 8 weeks in a crossover setting. Serum lipids and adipose tissue mRNA expression were measured during the diet intervention. At baseline, subjects with the Ala12Ala genotype had higher levels of HDL cholesterol and lower levels of LDL cholesterol, total triglycerides, and apolipoprotein B compared to those subjects with the Pro12Pro genotype (P\0.05, FDR\0.1). The Ala12Ala genotype also associated with higher mRNA expression of PPARG2, LPIN1, and SREBP-1c compared to participants with the Pro12Pro genotype (FDR\0.001). On the other hand, PUFA diet resulted in lower levels of fasting glucose, total cholesterol, total triglycerides, and apolipoprotein B (P\0.05, FDR\0.1) but did not affect PPARG2 mRNA expression in adipose tissue. We conclude that individuals with the Pro12Pro genotype, with higher triglyceride levels at baseline, are more likely to benefit from the PUFA diet. However, the beneficial effects of dietary PUFA and the Ala12Ala genotype of PPARG on serum lipids are mediated through divergent mechanisms. [ABSTRACT FROM AUTHOR]

Plasma fatty acid (FA) composition is known to be an indicator of dietary fat quality, but the associations of other dietary factors with plasma FA composition remain unknown in children. We investigated the cross-sectional associations of food consumption with the proportions of FA and estimated desaturase activities in plasma cholesteryl esters (CE) and phospholipids (PL) among children. The subjects were a population sample of 423 children aged 6-8 years examined at baseline of The Physical Activity and Nutrition in Children (PANIC) Study. We assessed food consumption by food records and plasma FA composition by gas chromatography. We used linear regression models adjusted for age, sex, physical activity and total energy intake to analyze the associations. A higher consumption of vegetable oil-based margarine (fat 60-80 %) was associated with a higher proportion of linoleic and α-linolenic acids in plasma CE and PL. A higher consumption of high-fiber grain products was related to a lower proportion of oleic acid in CE and PL. The consumption of candy was directly associated with the proportion of palmitoleic and oleic acid in plasma CE. The consumption of vegetable oil-based margarine was inversely associated with estimated stearoyl-CoA-desaturase activity in plasma CE and PL and the consumption of candy was directly related to it in plasma CE. The results of our study suggest that plasma FA composition is not only a biomarker for dietary fat quality but also reflects the consumption of high-fiber grain products and foods high in sugar among children. [ABSTRACT FROM AUTHOR]

Background Lower levels of physical activity (PA) and sedentary behaviour (SB) have been associated with increased cardiometabolic risk among children. However, little is known about the independent and combined associations of PA and SB as well as different types of these behaviours with cardiometabolic risk in children. We therefore investigated these relationships among children. Methods The subjects were a population sample of 468 children 6-8 years of age. PA and SB were assessed by a questionnaire administered by parents and validated by a monitor combining heart rate and accelerometry measurements. We assessed body fat percentage, waist circumference, blood glucose, serum insulin, plasma lipids and lipoproteins and blood pressure and calculated a cardiometabolic risk score using population-specific Z-scores and a formula waist circumference + insulin + glucose + triglycerides - HDL cholesterol + mean of systolic and diastolic blood pressure. We analysed data using multivariate linear regression models. Results Total PA was inversely associated with the cardiometabolic risk score (β = -0.135, p = 0.004), body fat percentage (β = -0.155, p < 0.001), insulin (β = -0.099, p = 0.034), triglycerides (β = -0.166, p < 0.001), VLDL triglycerides (β = -0.230, p < 0.001), VLDL cholesterol (β = -0.168, p = 0.001), LDL cholesterol (β = -0.094, p = 0.046) and HDL triglycerides (β = -0.149, p = 0.004) and directly related to HDL cholesterol (β = 0.144, p = 0.002) adjusted for age and gender. Unstructured PA was inversely associated with the cardiometabolic risk score (β = -0.123, p = 0.010), body fat percentage (β = -0.099, p = 0.027), insulin (β = -0.108, p = 0.021), triglycerides (β = -0.144, p = 0.002), VLDL triglycerides (β = -0.233, p < 0.001) and VLDL cholesterol (β = -0.199, p < 0.001) and directly related to HDL cholesterol (β = 0.126, p = 0.008). Watching TV and videos was directly related to the cardiometabolic risk score (β = 0.135, p = 0.003), body fat percentage (β = 0.090, p = 0.039), waist circumference (β = 0.097, p = 0.033) and systolic blood pressure (β = 0.096, p = 0.039). Resting was directly associated with the cardiometabolic risk score (β = 0.092, p = 0.049), triglycerides (β = 0.131, p = 0.005), VLDL triglycerides (β = 0.134, p = 0.009), VLDL cholesterol (β = 0.147, p = 0.004) and LDL cholesterol (β = 0.105, p = 0.023). Other types of PA and SB had less consistent associations with cardiometabolic risk factors. Conclusions The results of our study emphasise increasing total and unstructured PA and decreasing watching TV and videos and other sedentary behaviours to reduce cardiometabolic risk among children. Trial registration ClinicalTrials.gov Identifier: NCT01803776. [ABSTRACT FROM AUTHOR]

Background: The significance of erythrocyte membrane fatty acids (EMFAs) and their ratios to predict hyperglycemia and incident type 2 diabetes is unclear. Objective: We investigated EMFAs as predictors of the worsening of hyperglycemia and incident type 2 diabetes in a 5-y follow-up of a population-based study. Design: We measured EMFAs in 1346 Finnish men aged 45-73 y at baseline [mean ± SD age: 55 ± 6 y; body mass index (in kg/m2): 26.5 ± 3.5]. Our prospective follow-up study included only men who were nondiabetic at baseline and who had data available at the 5-y follow-up visit (n = 735). Results: Our study showed that, after adjustment for confounding factors, palmitoleic acid (16:1n-7; P = 2.8 × 10-7), dihomog- linolenic acid (20:3n-6; P = 2.3 × 10-4), the ratio of 16:1n-7 to 16:0 (P = 1.6 × 10-8) as a marker of stearoyl coenzyme A desaturase 1 activity, and the ratio of 20:3n-6 to 18:2n-6 (P = 9.4 × 10-9) as a marker of Δ6-desaturase activity significantly predicted the worsening of hyperglycemia (glucose area under the curve in an oral-glucose-tolerance test). In contrast, linoleic acid (18:2n-6; P = 0.0015) and the ratio of 18:1n-7 to 16:1n-7 (P = 1.5 × 10-9) as a marker of elongase activity had opposite associations. Statistical significance persisted even after adjustment for baseline insulin sensitivity, insulin secretion, and glycemia. Palmitoleic acid (P = 0.010) and the ratio of 16:1n-7 to 16:0 (P = 0.004) nominally predicted incident type 2 diabetes, whereas linoleic acid had an opposite association (P = 0.004), and n23 polyunsaturated fatty acids did not show any associations. Conclusion: EMFAs and their ratios are associated longitudinally with changes in glycemia and the risk type 2 diabetes [ABSTRACT FROM AUTHOR]

Erythrocyte membrane fatty acid (EMFA) composition is used in the validation of food frequency questionnaires (FFQ) and the evaluation of dietary fat quality. In this cross-sectional study we aimed to investigate associations of diet with EMFA. Altogether, 1,033 randomly selected Finnish men, aged from 47 to 75 years filled in a FFQ and their EMFA composition was analyzed. Marine polyunsaturated fatty acid (PUFA) intake correlated positively with erythrocyte eicosapentaenoic and docosahexaenoic acids ( r = 0.415 and r = 0.340, respectively, P < 0.001) and inversely with all n-6 PUFA analyzed ( P < 0.001). PUFA intake from spreads and cooking fats correlated positively with alpha-linolenic (ALA), linoleic (LNA) and nervonic acids ( r = 0.229, r = 0.160 and r = 0.143, respectively, P < 0.001). Milk fat intake was associated with myristic and behenic acids ( r = 0.186 and r = 0.132, respectively P < 0.001). Butter users had lower ALA and LNA proportions (mol%) than non-users (0.16 ± 0.04 vs. 0.19 ± 0.05, P < 0.001 and 7.77 ± 1.02 vs. 8.12 ± 1.11, P = 0.001). Higher PUFA intake from meat was related to decreased long-chain n-3 ( P < 0.001) and increased n-6 PUFA ( P < 0.001) proportions. In conclusion, EMFA composition reflects particularly well the intakes of n-3 PUFA, whereas other associations remained lower. Yet, all main sources of dietary fat were related with EMFA. The dietary effect on the nervonic acid proportion was confirmed. [ABSTRACT FROM AUTHOR]

Background: The effect of weight loss on different plasma lipid subclasses at the molecular level is unknown. The aim of this study was to examine whether a diet-induced weight reduction result in changes in the extended plasma lipid profiles (lipidome) in subjects with features of metabolic syndrome in a 33-week intervention. Methodology/Principal Findings: Plasma samples of 9 subjects in the weight reduction group and 10 subjects in the control group were analyzed using mass spectrometry based lipidomic and fatty acid analyses. Body weight decreased in the weight reduction group by 7.8±2.9% (p,0.01). Most of the serum triacylglycerols and phosphatidylcholines were reduced. The decrease in triacylglycerols affected predominantly the saturated short chain fatty acids. This decrease of saturated short chain fatty acid containing triacylglycerols correlated with the increase of insulin sensitivity. However, levels of several longer chain fatty acids, including arachidonic and docosahexanoic acid, were not affected by weight loss. Levels of other lipids known to be associated with obesity such as sphingolipids and lysophosphatidylcholines were not altered by weight reduction. Conclusions/Significance: Diet-induced weight loss caused significant changes in global lipid profiles in subjects with abnormal glucose metabolism. The observed changes may affect insulin sensitivity and glucose metabolism in these subjects. [ABSTRACT FROM AUTHOR]

Background: Carbohydrate modification based on rye bread and pasta enhances early insulin secretion in subjects with the metabolic syndrome. Objective: Because the actions of insulin and cholesterol metabolism are interrelated, the question is raised of whether it is possible to alter cholesterol metabolism by means of dietary carbohydrate modification. Design: We investigated the 12-wk effects of dietary carbohydrate modification on cholesterol synthesis and absorption by measuring the ratios of surrogate markers of precursor (cholestenol, desmosterol, and lathosterol) and absorption (cholestanol and plant sterols) sterols to cholesterol and their association to glucose metabolism in 74 subjects with the metabolic syndrome. The subjects were randomly assigned to diets with rye bread and pasta (RPa) or oat, wheat bread, and potato(OWPo)as the main carbohydrate source (34% and 37% of energy intake, respectively). Results: During the study, serum cholesterol concentrations remained unchanged. Cholesterol synthesis was lower (6-10% for cholestenol and lathosterol; P < 0.05) and absorption higher (9%; P<0.05 for sitosterol) with the OWPo diet than at baseline. With the RPa diet, cholesterol absorption was lower and synthesis higher than with the OWPo diet. The increment in the glucose area under the curve with the RPa diet was positively related to baseline cholesterol synthesis (eg, lathosterol; r = 0.480, P < 0.05) and negatively to absorption (for cholestanol; r=-0.520, P<0.05). In the combined group, the changes in the cholestanol ratio and the insulinogenic index were interrelated (r=-0.464, P < 0.001). Conclusions: Carbohydrate modifications had dissimilar effects on cholesterol metabolism. Consumption of RPa, as compared with OWPo, may be clinically more favorable because it seems to inhibit the absorption of cholesterol, a factor crucial in the development of arterial atherosclerosis. [ABSTRACT FROM AUTHOR]

Triacylglycerols secreted by liver and carried by very low density lipoprotein (VLDL) are hydrolysed in circulation by lipoprotein and hepatic lipases. These enzymes have been shown to have positional and fatty acid specificity in vitro . If there were specificity in basal lipolysis in vivo , triacylglycerol compositions of circulating and newly secreted VLDL would be different. To study this we compared the composition of normal fasting VLDL triacylglycerol of Wistar rats to that obtained after blocking lipolysis by Triton WR1339, which increased plasma VLDL triacylglycerol concentration about 4.7-fold in 2 h. Analyses of molecular species of sn -1,2- and sn -2,3-diacylglycerol moieties and stereospecific triacylglycerol analysis revealed major differences between the groups in the VLDL triacylglycerol composition. In nontreated rats, the proportion of 16:0 was higher and that of 18:2n-6 lower in the sn -1 position. The proportion of 14:0 was lower in all positions and that of 18:0 was lower in the sn -1 and sn -3 positions in nontreated rats whereas the proportions of 20:4n-6, 20:5n-3, 22:5n-3 and 22:6n-3 were higher in the sn -1 and lower in the sn -2 position. These results suggest that the fatty acid of the sn -1 position is the most decisive factor in determining the sensitivity for hydrolysis of the triacylglycerol. In addition, triacylglycerol species with highly unsaturated fatty acids in the sn -2 position also favoured hydrolysis. The in vivo substrate specificity followed only partly that obtained in in vitro studies indicating that the nature of molecular association of fatty acids in natural triacylglycerol affects its susceptibility to lipolysis. To conclude, our results indicate that preferential basal lipolysis leads to major structural differences between circulating and newly secreted VLDL triacylglycerol. These differences extend beyond those anticipated from analysis of total fatty acids and constitute a previously unrecognized feature of... [ABSTRACT FROM AUTHOR]

Background: The affinity of intestinal fatty acid binding protein (FABP) for fatty acids is regulated by the polymorphism at codon 54 of the FABP2 gene (alanine-to-threonine shift). We found earlier that the threonine-encoding allele (Thr54) is associated with an increased postprandial lipemic response. Objective: We studied the postprandial responses of individual fatty acids in subjects homozygous for the Thr54 or alanineencoding allele (Ala54). Design: Oral-fat-loading tests were performed in 8 subjects homozygous for Thr54 and in 7 subjects homozygous for Ala54. Results: The postprandial responses of most of the 14-18-carbon fatty acids in chylomicron and VLDL triacylglycerols were significantly elevated in the Thr54 homozygotes whereas the relative increases in these fatty acids were not significantly different in both groups. The amounts of 20- and 22-carbon polyunsaturated fatty acids started to increase later than the amounts of shorter ones after the test meal, and the differences between the groups were mostly insignificant. The responses of chylomicron fatty acids correlated positively with postprandial insulin response in the Thr54 homozygotes and inversely in the Ala54 homozygotes. VLDL fatty acid responses correlated with fasting triacylglycerol concentrations in the Ala54 homozygotes but not in the Thr54 homozygotes. Conclusion: The threonine-encoding allele of the FABP2 gene is associated with an increased postprandial response of 14-18-carbon fatty acids but not with changes in the relative amounts of individual fatty acids introduced to chylomicron triacylglycerols. [ABSTRACT FROM AUTHOR]

Trans fatty acids may be involved in atherosclerotic vascular diseases. We investigated the incorporation of dietary trans fatty acids and oleic acid into the serum triglycerides (TG), cholesterol esters (CE), and phospholipids (PL). Fourteen healthy female volunteers, aged 23.2±3.1 yr (mean±SD), body mass index 20.8±2.1 kg/m2 participated in this study. All subjects consumed both a trans fatty acid-enriched diet (TRANS diet) and an oleic acid-enriched diet (OLEIC diet) for 4 wk according to a randomized crossover design. Both experimental diet periods were preceded by consumption of a baseline diet for 2 wk which supplied 37% of total energy (E%) as fat: 18 E% from saturated fatty acids (SFA), 12 E% from monounsaturated fatty acids, and 6 E% from polyunsaturated fatty acids. Five E% of the SFA in the baseline diet was replaced by trans fatty acids (18∶1 t and 18∶2 c,t+18∶2 t,t, where c is cis and t is trans) in the TRANS diet and by oleic acid (18∶1n-9) in the OLEIC diet. After the TRANS diet, the proportions of 18∶1 t and 18∶2 t increased ( P <0.001) in all serum lipid fractions analyzed. The increase of 18∶1 t in TG and PL (1.80±0.28 vs. 5.26±1.40; 1.07±0.34 vs. 3.39±0.76 mol% of total fatty acids, respectively) was markedly higher than that in CE (0.44±0.07 vs. 0.92±0.26), whereas that of 18∶2 t was nearly the same in all three fractions. The proportions of palmitic, stearic, arachidonic, and eicosapentaenoic acids in TG, CE, and PL and that of oleic acid in TG and CE were decreased when compared with the baseline value. In contrast, the proportion of palmitoleic acid in TG and PL and that of linoleic acid in PL increased on the TRANS diet. After consumption of the OLEIC diet, the proportion of oleic acid increased in all three lipid fractions analyzed, and the percentage increase was nearly the same in all fractions. In contrast, the proportions of 18∶1 t in TG and PL and 18∶2 t in TG and CE decreased when compared with the baseline value. In conclusion, a moderate increase in dietary trans fatty acids resulted in a marked incorporation into serum lipids and decreased the conversion of linoleic acid to its more unsaturated long-chain metabolites. Analysis of 18∶1 t from serum TG and PL seems to reflect reliably the dietary intake of this fatty acid. [ABSTRACT FROM AUTHOR]

The effects of n-3 fatty acid supplementation in the form of fresh fish, fish oil, and docosahexaenoic acid (DHA) oil on the fatty acid composition of plasma lipid fractions, and platelets and erythrocyte membranes of young healthy male students were examined. Altogether 59 subjects (aged 19–32 yr, body mass index 16.8–31.3 kg/m2) were randomized into the following diet groups: (i) control group; (ii) fish diet group eating fish meals five times per week [0.38±0.04 g eicosapentaenoic acid (EPA) and 0.67±0.09 g DHA per day]; (iii) DHA oil group taking algae-derived DHA oil capsules (1.68 g/d DHA oil group taking algae-derived DHA oil capsules (1.68 g/d DHA in triglyceride form); and (iv) fish oil group (1.33 g EPA and 0.95 g DHA/d as free fatty acids) for 14 wk. The fatty acid composition of plasma lipids, platelets, and erythrocyte membranes was analyzed by gas chromatography. The subjects kept 4-d food records four times during the study to estimate the intake of nutrients. In the fish diet, in DHA oil, and in fish oil groups, the amounts of n-3 fatty acids increased and those of n-6 fatty acids decreased significantly in plasma lipid fractions and in platelets and erythrocyte membranes. A positive relationship was shown between the total n-3 polyunsaturated fatty acids (PUFA) and EPA and DHA intake and the increase in total n-3 PUFA and EPA and DHA in all lipid fractions analyzed. DHA was preferentially incorporated into phospholipid (PL) and triglyceride (TG) and there was very little uptake in cholesterol ester (CE), while EPA was preferentially incorporated into PL and CE. The proportion of EPA in plasma lipids and platelets and erythrocyte membranes increased also by DHA supplementation, and the proportion of linoleic acid increased in platelets and erythrocyte membranes in the DHA oil group as well. These results suggest retroconversion of DHA to EPA and that DHA also interferes with linoleic acid metabolism. [ABSTRACT FROM AUTHOR]

The fatty acid composition of erythrocytes, platelets, and serum lipids was compared between subjects who had been eating a strict uncooked vegan diet ('living food') for years and omnivore controls. The vegan diet contains equal amounts of fat but more monounsaturated and polyunsaturated and less saturated fatty acids than the mixed diet of the control group. In vegans, the proportion of linoleic acid was greater in all lipid fractions studied. Also, the levels of other n−6 fatty acids were greater, with the exception of arachidonic acid levels, which were similar in most fractions. In erythrocytes, platelets and serum phospholipid fractions, this increase was mainly at the expense of the n−3 fatty acids. The proportions of eicosapentaenoic and docosahexaenoic acid were only 29-36% and 49-52% of those in controls, respectively. In vegans the ratio of n−3 to n−6 fatty acids was only about half that in omnivores. In addition to the lower levels of n−3 fatty acids, the proportions of palmitic and stearic acids were lower in serum cholesteryl esters, triglycerides and free fatty acids of vegans. The proportion of oleic acid was slightly lower only in serum cholesteryl esters and erythrocyte phosphatidylserine. The results show that, in the long term, the vegan diet has little effect on the proportions of oleic and arachidonic acids, whereas the levels of n−3 fatty acids are depressed to very low levels with prolonged consumption of the high linoleic and oleic acid components of this diet. [ABSTRACT FROM AUTHOR]

Dietary adherence to four different fat-modified diets was examined in 160 subjects by determining the fatty acid composition of serum cholesterol esters (CEs) and erythrocyte (ER) and platelet (PT) membranes in addition to food records. Subjects were randomly assigned to one of the following diet groups: 1) high-sat-35/14:10:4 (% of energy from total/ saturated:monounsaturated:polyunsaturated fatty acids in the actual diet) 2) AHA (American Heart Association) type-32/ 10:8:8 3) monoene-enriched-34/11:11:5, or 4) low-fat-30/ 12:8:3 for 6 mo. Decreases in the proportions of palmitic acid in CEs were found in the AHA-type and monoene-enriched-diet groups. An increased proportion of linoleic acid in CEs was found in the AHA-type group. The differences in the proportions of palmitic acid in CEs and linoleic and palmitoleic acids in PTs were significant in the AHA-type and monoene-enriched-diet groups compared with the high-sat group. An increase in α-linolenic acid in CEs was an indicator of the use of low erucic acid rapeseed oil, which was the main source of monoenes in the monoene-enriched-diet group. [ABSTRACT FROM AUTHOR]

Objective: Fatty acid (FA) composition affects obesity-associated low-grade inflammation. It has been shown that the fatty acid desaturase (FADS) 2 gene polymorphism associates with FA metabolism and adipose tissue (AT) inflammation. This study aimed to investigate the relationship between FA metabolism and inflammation in different tissues and the possible interorgan cross talk.Methods: Cross-sectional baseline data from 155 individuals with obesity (both male and female) participating in the Roux-en-Y gastric bypass operation in the ongoing Kuopio Obesity Surgery Study were used. Gas chromatograph for FA composition, liver histology, and targeted RNA expression for gene expression profile were performed.Results: It was demonstrated that the saturated fatty acid (SFA) proportion in AT correlated positively with inflammation in subcutaneous AT (SAT) and visceral AT (VAT) but not in the liver, while the monounsaturated fatty acid (MUFA) proportion in SAT and VAT correlated negatively with AT inflammation. Notably, there was a positive correlation between AT n-6 polyunsaturated fatty acids (PUFAs), but not AT SFAs or MUFAs, and liver inflammation. This correlation was modified by the FADS2 genotype.Conclusions: The AT FA profile relates with AT inflammation. Additionally, there seems to be a complex interaction, partly regulated by the FADS2 genotype, regulating the interaction between FAs in AT and liver inflammation. [ABSTRACT FROM AUTHOR]