8-11-14-eicosatrienoic-acid and palmitoleic-acid

Thirty-one children, selected for marked inattention and overactivity, were studied in a double-blind, placebo-controlled crossover study of essential fatty acid (EFA) supplementation. Subjects received the active treatment and placebo conditions for 4 weeks each and were assessed on a variety of cognitive, motor, and standardized rating scale measures. EFA supplementation (evening primrose oil; Efamol) resulted in significantly lower levels of palmitoleic acid (a nonessential fatty acid) and higher concentrations of dihomogammalinolenic acid, an EFA previously found to be deficient in some hyperactive children. Supplementation was also associated with significant changes on two performance tasks and with significant improvement to parent ratings on the subscales designated as Attention Problem and Motor Excess of the Revised Behavior Problem Checklist. However, a variety of eight other psychomotor performance tests and two standardized teacher rating scales failed to indicate treatment effects. When the experiment-wise probability level was set at .05, only 2 of 42 variables showed treatment effects. Baseline EFA concentrations appeared to be unrelated to treatment response. It was concluded that EFA supplementation, as employed here, produces minimal or no improvements in hyperactive children selected without regard to baseline EFA concentrations.

Topics: 8,11,14-Eicosatrienoic Acid; Attention Deficit Disorder with Hyperactivity; Child; Clinical Trials as Topic; Double-Blind Method; Fatty Acids, Essential; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Oenothera biennis; Palmitic Acids; Plant Oils; Psychomotor Performance

The obese lipid profile is associated with increased free fatty acids and triacylglycerides. Currently, little is known about the plasma lipid species associated with obesity. In this study, we compared plasma lipid fatty acid (FA) profiles as a function of BMI. Profiling phospholipid (PL) FAs and their respective oxylipids could predict which obese individuals are more likely to suffer from diseases associated with chronic inflammation or oxidative stress. We investigated the relationship between BMI and plasma PL (PPL) FA composition in 126 men using a quantitative gas chromatography analysis. BMI was inversely associated with both PPL nervonic and linoleic acid (LA) but was positively associated with both dihomo-γ-linolenic and palmitoleic acid. Compared to lean individuals, obese participants were more likely to have ω-6 FAs, except arachidonic acid and LA, incorporated into PPLs. Obese participants were less likely to have EPA and DHA incorporated into PPLs compared to lean participants. Non-esterified plasma PUFA and oxylipid analysis showed ω-6 oxylipids were more abundant in the obese plasma pool. These ω-6 oxylipids are associated with increased angiogenesis (i.e. epoxyeicosatrienoates), reactive oxygen species (i.e. 9-hydroxyeicosatetraenoate), and inflammation resolution (i.e. Lipoxin A4). In summary, BMI is directly associated with specific PPL FA and increased ω-6 oxylipids.

Topics: 8,11,14-Eicosatrienoic Acid; Aged; Body Mass Index; Chromatography, Gas; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Humans; Linoleic Acid; Male; Middle Aged; Obesity; Triglycerides

The significance of erythrocyte membrane fatty acids (EMFAs) and their ratios to predict hyperglycemia and incident type 2 diabetes is unclear.. 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.. We measured EMFAs in 1346 Finnish men aged 45-73 y at baseline [mean ± SD age: 55 ± 6 y; body mass index (in kg/m(2)): 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).. Our study showed that, after adjustment for confounding factors, palmitoleic acid (16:1n-7; P = 2.8 × 10(-7)), dihomo-γ-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(-7)) as a marker of Δ(6)-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 n-3 polyunsaturated fatty acids did not show any associations.. EMFAs and their ratios are associated longitudinally with changes in glycemia and the risk type 2 diabetes.

Topics: 8,11,14-Eicosatrienoic Acid; Aged; Biomarkers; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Erythrocyte Membrane; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Finland; Follow-Up Studies; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Linear Models; Linoleic Acid; Male; Middle Aged; Prospective Studies; Risk Factors; Stearoyl-CoA Desaturase; White People

Because alterations in blood fatty acid (FA) composition by dietary lipids are associated with insulin resistance and related metabolic disorders, we hypothesized that serum phospholipid FA composition would reflect the early alteration of fasting glycemic status, even in people without metabolic syndrome (MetS). To examine this hypothesis, serum phospholipid FA, desaturase activities, fasting glycemic status, and cardiometabolic parameters were measured in study participants (n = 1022; 30-69 years; male, n = 527; female, n = 495; nondiabetics without disease) who were stratified into normal fasting glucose (NFG) and impaired fasting glucose (IFG) groups. Total monounsaturated FA (MUFA), oleic acid (OA; 18:1n-9), dihomo-γ-linolenic acid (DGLA; 20:3n-6), Δ-9-desaturase activity (D9D; 18:1n-9/18:0), and DGLA/linoleic acid (20:3n-6/18:2n-6) in serum phospholipids were significantly higher in IFG subjects than NFG controls. Study subjects were subdivided into 4 groups, based on fasting glucose levels and MetS status. Palmitoleic acid (16:1n-7) was highest in IFG-MetS and lowest in NFG-non-MetS subjects. Oleic acid and D9D were higher in IFG-MetS than in the other 3 groups. Dihomo-γ-linolenic acid and DGLA/linoleic acid were higher in MetS than in non-MetS, regardless of fasting glucose levels. The high-sensitivity C-reactive proteins (hs-CRPs) and 8-epi-prostaglandin-F2α were higher in IFG than in NFG, regardless of MetS status. Oxidized low-density lipoproteins were higher in IFG-MetS than in the other 3 groups. Total MUFAs, OA, and D9D were positively correlated with homeostasis model assessment of insulin resistance, fasting glucose, triglyceride, hs-CRP, and 8-epi-prostaglandin-F2α. Palmitoleic acid was positively correlated with triglyceride and hs-CRP. Lastly, total MUFA, OA, palmitoleic acid, and D9D were associated with early alteration of fasting glycemic status, therefore suggesting that these may be useful markers for predicting the risk of type 2 diabetes and cardiometabolic diseases.

Topics: 8,11,14-Eicosatrienoic Acid; Biomarkers; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dinoprost; Fasting; Fatty Acids, Monounsaturated; Female; Humans; Insulin; Insulin Resistance; Linoleic Acid; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Oleic Acid; Phospholipids; Stearoyl-CoA Desaturase; Triglycerides

The association of fatty acid composition with insulin resistance and type 2 diabetes has been reported in Western populations, but there is limited evidence of this association among the Japanese, whose populace consume large amounts of fish. To test the hypothesis that high palmitic, palmitoleic, and dihomo-γ-linolenic acids and low levels of linoleic and n-3 fatty acids are associated with higher insulin resistance among the Japanese, the authors investigated the relationship between serum fatty acid composition and serum C-peptide concentrations in 437 Japanese employees aged 21 to 67 years who participated in a workplace health examination. Serum cholesterol ester and phospholipid fatty acid compositions were measured by gas-liquid chromatography. Desaturase activity was estimated by fatty acid product-to-precursor ratios. A multiple regression was used to assess the association between fatty acid and C-peptide concentrations. C-peptide concentrations were associated inversely with linoleic acid levels in cholesterol ester and phospholipid (P for trend = .01 and .02, respectively) and positively with stearic and palmitoleic acids in cholesterol ester (P for trend =.02 and .006, respectively) and dihomo-γ-linolenic acid in cholesterol ester and phospholipid (P for trend < .0001 for both). C-peptide concentrations were not associated with n-3 polyunsaturated fatty acids. C-peptide concentrations significantly increased as δ-9-desaturase (16:1 n-7/16:0) and δ-6-desaturase (18:3 n-6/18:2 n-6) increased (P for trend = .01 and .03, respectively) and δ-5-desaturase (20:4 n-6/20:3 n-6) decreased (P for trend = .004). In conclusion, a fatty acid pattern with high levels of serum stearic, palmitoleic, or dihomo-γ-linolenic acids; δ-9-desaturase (16:1 n-7/16:0) or δ-6-desaturase (18:3 n-6/18:2 n-6) activities; and low levels of serum linoleic acid or δ-5-desaturase (20:4 n-6/20:3 n-6) activity might be associated with higher insulin resistance in Japanese adults.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Aged; Asian People; C-Peptide; Cholesterol Esters; Chromatography, Gas; Cross-Sectional Studies; Delta-5 Fatty Acid Desaturase; Fatty Acid Desaturases; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Female; Humans; Insulin Resistance; Linoleic Acid; Linoleoyl-CoA Desaturase; Male; Middle Aged; Multivariate Analysis; Phospholipids; Regression Analysis; Stearic Acids; Stearoyl-CoA Desaturase; Young Adult

Alterations by perfluorinated fatty acids (PFCAs) with a chain length of 6-9 carbons in the fatty acid profile of hepatic lipids of mice were investigated. The characteristic changes caused by all the PFCAs examined were increases in the contents and proportions of oleic acid (18 : 1), palmitoleic acid (16 : 1) and 8,11,14-eicosatrienoic acid (20 : 3) in hepatic lipids. Hepatic contents of palmitic acid were also increased by the treatments with the PFCAs. These effects were almost dependent on the hepatic concentrations of PFCA molecules regardless of their carbon chain length. Perfluorooctanoic acid elevated the expressions of mRNA encoding acetyl-CoA carboxylase, fatty acid synthase, malic enzyme, stearoyl-CoA desaturase (SCD) (SCD1 and 2), chain elongase (ELOVL5), Δ6 desaturase (Fads2), 1-acylglycerophosphocholine acyltransferase (LPCAT) (LPCAT3). The four PFCAs examined induced microsomal SCD and LPCAT in hepatic concentration-dependent manners regardless of carbon chain length. One linear regression line was confirmed between LPCAT activity and hepatic concentration of PFCA at wide range of the concentration, whereas the induction of SCD was saturable at relatively low concentration of PFCAs. These results suggest (i) that PFCAs with a chain length of 6-9 carbons change the fatty acid profile of hepatic lipids by increasing contents and proportions of 16 : 1, 18 : 1 and 20 : 3, (ii) that these alterations in fatty acid profile are caused by up-regulation of SCD, de novo fatty acid synthesis, chain elongase and Δ6 desaturase and (iii) that the mechanism underlying SCD induction is, in part, mediated through peroxisome proliferator-activated receptor α.

Topics: 8,11,14-Eicosatrienoic Acid; Acetyltransferases; Animals; Caprylates; Dose-Response Relationship, Drug; Environmental Pollutants; Fatty Acid Elongases; Fatty Acids; Fatty Acids, Monounsaturated; Fluorocarbons; Gene Expression Regulation, Enzymologic; Hepatomegaly; Isoenzymes; Linoleoyl-CoA Desaturase; Liver; Male; Mice; Mice, Inbred Strains; Molecular Weight; Oleic Acid; PPAR alpha; RNA, Messenger; Stearoyl-CoA Desaturase

The determinants of the regio- and stereoselective oxidation of fatty acids by cytochrome P450 BM-3 were examined by mutagenesis of residues postulated to anchor the fatty acid or to determine its active site substrate-accessible volume. R47, Y51, and F87 were targeted separately and in combination in order to assess their contributions to arachidonic, palmitoleic, and lauric acid binding affinities, catalytic rates, and regio- and stereoselective oxidation. For all three fatty acids, mutation of the anchoring residues decreased substrate binding affinity and catalytic rates and, for lauric acid, caused a significant increase in the enzyme's NADPH oxidase activity. These changes in catalytic efficiency were accompanied by decreases in the regioselectivity of oxygen insertion, suggesting an increased freedom of substrate movement within the active site of the mutant proteins. The formation of significant amounts of 19-hydroxy AA by the Y51A mutant and of 11,12-EET by the R47A/Y51A/F87V triple mutant, suggest that wild-type BM-3 shields these carbon atoms from the heme bound reactive oxygen by restricting the freedom of AA displacement along the substrate channel, and active site accessibility. These results indicate that binding affinity and catalytic turnover are fatty acid carbon-chain length dependent, and that the catalytic efficiency and the regioselectivity of fatty acid metabolism by BM-3 are determined by active site binding coordinates that control acceptor carbon orientation and proximity to the heme iron.

Topics: 8,11,14-Eicosatrienoic Acid; Arachidonic Acid; Bacterial Proteins; Catalytic Domain; Cytochrome P-450 Enzyme System; Fatty Acids; Fatty Acids, Monounsaturated; Isoenzymes; Lauric Acids; Mixed Function Oxygenases; Mutagenesis, Site-Directed; NADPH Oxidases; NADPH-Ferrihemoprotein Reductase; Oxidation-Reduction; Stereoisomerism; Substrate Specificity

Delta 9, delta 6 and delta 5 desaturation activity and the thioesterification of eicosa-8,11,14-trienoic acid (DGLA) were measured in spontaneously hypertensive rats (SHR) compared to normotensive controls (WKY). SHR exhibited lower levels in the long-chain fatty acyl-CoA (LCFA) synthetase and in delta 6 and delta 5 desaturase activities in liver. The enzymatic activity changes were reflected on the fatty acid composition of liver microsomes. In testis, the thioesterification of DGLA and its conversion to arachidonic acid, (AA), at the delta 5 desaturation step were also depressed in SHR. We conclude that, in SHR, the alteration in polyunsaturated fatty acid (PUFA) metabolism may influence the synthesis of AA-derived eicosanoids involved in the control of blood pressure regulation.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acid; Fatty Acids, Monounsaturated; Hypertension; Male; Microsomes, Liver; Palmitic Acid; Rats; Rats, Inbred SHR; Rats, Inbred WKY

The effect of insulin on the oxidative desaturation of 1-14C palmitic acid to palmitoleic acid (delta 9 desaturase) 1-14C linoleic acid to alpha-linolenic acid (delta 6 desaturase) on rat liver microsomes and 1-14C eicosa-8,11,14-trienoic acid to arachidonic acid (delta 5 desaturase) on rat liver microsomes and hepatoma tissue culture (HTC) cells was studied. After 12 h of insulin injection, at a dose of 2.5-12.5 U/kg no change was found in delta 9 desaturation activity while delta 5 desaturation activity decreased. The conversion of linoleic to alpha-linolenic acid decreased when the amount of insulin injected was 5 U/kg or more. The effect of insulin (5 U/kg) on delta 9, delta 6 or delta 5 desaturation activity was tested from 1 to 12 h after the injection. The conversion of palmitic acid to palmitoleic acid showed no important changes along the time, while delta 5 desaturation activity decreased at all the times tested. delta 6 Desaturation activity showed a slight increase after 1 h of insulin treatment and then decreased significantly up to the end of the experiment. The addition of 400 mU/ml or more of insulin to the incubation medium of HTC cells produced a significant decrease on the conversion of eicosatrienoic acid to arachidonic acid. The effect of insulin on fatty acid desaturation activity of liver microsomes of normal rats differs from that of diabetic rats. The role of this hormone in relation to other hormones, carbohydrate metabolism and lipid biosynthesis on the activity of the desaturases was discussed.

Topics: 8,11,14-Eicosatrienoic Acid; alpha-Linolenic Acid; Animals; Arachidonic Acids; Blood Glucose; Cells, Cultured; Delta-5 Fatty Acid Desaturase; Fatty Acid Desaturases; Fatty Acids, Monounsaturated; Female; Insulin; Linoleic Acid; Linoleic Acids; Linolenic Acids; Linoleoyl-CoA Desaturase; Liver; Liver Neoplasms, Experimental; Palmitic Acids; Rats; Stearoyl-CoA Desaturase