D6D Activity Research Articles

Plasma Lipidomic n-6 Polyunsaturated Fatty Acids and Type 2 Diabetes Risk in the EPIC-Potsdam Prospective Cohort Study.

Evidence on plasma n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk is inconsistent. We examined the associations of lipid class-specific PUFA concentrations with type 2 diabetes risk. In the prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (nested case-cohort study: subcohort 1,084 participants, 536 participants with type 2 diabetes, median follow-up 6.5 years), we measured plasma 18:2, 20:3, and 20:4 concentrations in 12 lipid (sub)classes, likely reflecting the plasma concentrations of linoleic acid (18:2n-6), dihomo-γ-linolenic acid (20:3n-6), and arachidonic acid (20:4n-6). The Δ-5 desaturase (D5D) activity was estimated as the 20:4/20:3 ratio. Associations with diabetes were estimated with Cox proportional hazards models. Higher concentrations of 18:2 were inversely associated with type 2 diabetes risk, particularly in lysophosphatidylcholines (hazard ratio [HR] per 1 SD 0.53; 95% CI 0.23-1.26) and monoacylglycerols (HR 0.59; 0.38-0.92). Higher concentrations of 20:3 in phospholipid classes phosphatidylcholines (HR 1.63; 1.23-2.14), phosphatidylethanolamines (HR 1.87; 1.32-2.65), and phosphatidylinositol (HR 1.40; 1.05-1.87); free fatty acids (HR 1.44; 1.10-1.90); and cholesteryl esters (HR 1.47; 1.09-1.98) were linked to higher type 2 diabetes incidence, and these associations remained statistically significant after correction for multiple testing. Higher 20:4 concentrations were not associated with risk. The estimated D5D activity in phospholipids and cholesteryl esters was associated with lower type 2 diabetes risk. Single nucleotide polymorphisms in the D5D-encoding FADS genes explained relatively high proportions of variation of estimated D5D activity in those lipid classes. Plasma n-6 PUFAs were associated differently with type 2 diabetes, depending on fatty acid and the lipid class.

Plasma phospholipid fatty acid profile, estimated desaturase activities and prevalence of the metabolic syndrome in a general population cohort: A cross-sectional study

BACKGROUND: An altered plasma fatty acid (FA) profile and desaturase activities have been associated with several metabolic diseases, including the MetS, but studies in the general populations are lacking, and only few studies have investigated a broad spectrum of FA in plasma phospholipids (PL). OBJECTIVE: We investigated, cross-sectionally, the relationship of the FA profile and desaturase activities in plasma PL with the prevalence of MetS in a general population in The Netherlands. METHODS: Baseline characteristic data from 850 participants (male: 50.2%) aged 38-68 years recruited in the Lifelines cohort study were obtained. The FA profile was determined in fasting plasma PL, and desaturase activities were estimated from product/precursor ratios. The MetS was defined according to International Diabetes Federation. Logistic regressions were used to examine the relation of the FA profile with the prevalence of MetS, and Bonferroni correction was applied to account for multiple testing. RESULTS: 151 participants (17.7%) had the MetS. After adjustment for several confounders and Bonferroni correction, higher tertiles of C18 : 0 (the early precursor of de novo lipogenesis pathway), C18 : 3n6 and C20 : 3n6 (both consistent with a high Δ6 desaturase (D6D) activity), and D6D activity itself were associated with a higher prevalence of MetS, while higher tertiles of C18 : 1n7, C24 : 0, and C24 : 1n9 (very long chain FA) as well as stearoyl-CoA desaturase (SCD)-18 were inversely associated with the MetS. CONCLUSIONS: This study shows that a wide-ranging plasma PL FA profile and estimated desaturase activities were different between adults with and without the MetS in a general representative population and implicates the importance of monitoring individual FAs and desaturase activities as novel modifiable biomarkers for the MetS.

Relationship between estimated desaturase enzyme activity and metabolic syndrome in a longitudinal study.

Desaturase enzyme activities (DEA) are associated with several metabolic diseases. The aim of the present study was to assess the relationship between estimated plasma DEA and the metabolic syndrome (MetS), as well as their relationship with individual components of the MetS. We conducted a longitudinal study of 148 participants recruited at random from the PREDIMED trial (Hospital Clinic site). At baseline and after 1 year of follow-up, DEA were estimated from product/precursor ratios of individual plasma fatty acids. Logistic regressions were used to assess the relationship of estimated DEA MetS, adjusted for potential cofounders. Estimated Δ5 desaturase (D5D) activity was associated with lower risk of MetS, whereas stearoyl-CoA (SCD)-16 and SCD-18 were negatively associated with MetS status. SCD-16, SCD-18, and Δ6 desaturase (D6D) were positively associated with triglycerides, SCD-18 was inversely associated with HDL-cholesterol. Estimated D6D activity was found to be associated with increases in diastolic blood pressure. In contrast, D5D was negatively associated with triglycerides, diastolic blood pressure and waist circumference. The present longitudinal study suggests that estimated SCD-16, SCD-18, and D6D have a negative impact in MetS and its components, whereas D5D may have beneficial effects for metabolic health.

475-P: Plasma Fatty Acid Composition Is Associated with Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Patients

Type 2 diabetes is frequently complicated by nonalcoholic fatty liver disease (NAFLD) , which is mainly caused by high-fat and high-calorie diets, and obesity. In this regard, both the quantity and quality of fat accumulating in the liver are important, and in particular, the proportion of each fatty acid may be an important biomarker for NAFLD. We investigated whether serum fatty acid composition, especially n-6 polyunsaturated fatty acid (PUFA) and, saturated fatty acid (MUFA) and desaturase activity are associated with NAFLD in type 2 diabetes patients. Eighty-five type 2 diabetes patients (age: 60.3±13.9 years, BMI 27.5±5.8 kg/m2) who had no history of alcohol drinking, and had a negative result for hepatitis viruses were included as study subjects. Fatty liver (FL) was diagnosed based on liver ultrasonographic findings. Patients with FL were included in the FL group (n=51) , whereas those without FL included in the non-FL group (n=34) . Serum fatty acid levels were measured using gas chromatography. Desaturase activity for n-6 PUFAs was calculated as the ratio of arachidonic acid to dihomo-gamma-linolenic acid (DGLA) for Δ5 desaturase (D5D) . Waist circumference, BMI, serum triglyceride (TG) concentration, and ALT level were significantly higher in the FL group than in the non-FL group. The FL group also demonstrated higher levels of palmitic acid (PAL) and stearic acid (STA) , PAL/STA ratio, and DGLA than the non-FL group. In the FL group D5D activity was significantly lower than that in the non-FL group. PAL level, DGLA, and PAL/STA ratio showed a significant positive correlation with TG and ALT levels. Multiple regression analysis showed that DGLA was independently associated with FL development. These results suggest that type 2 diabetes patients with NAFLD have changes in their blood fatty acid profile, especially increased DGLA and PAL levels. The high levels of blood DGLA indicate downregulation of n-6 PUFA metabolism, probably caused by the decreased activity of D5D. Disclosure M.Higa: None. T.Ichijo: None.

1234-P: Serum Fatty Acid Composition as a Biomarker of Diabetes Development: Tokushima Cohort Study

Few prospective cohort studies still exist on the association between serum fatty acid (FA) proportions and the enzymes involved in their synthesis and the onset of type 2 diabetes (T2D) . Thus, the aim of the present study was to investigate whether or not serum FA proportions or FA ratios, which reflect desaturase activities, are associated with the incidence of T2D. Here we analyzed data of a prospective cohort study, which was conducted during 2010-20in Japan. A total of 872 male workers without diabetes aged over 20 years were followed up prospectively. Diabetes was defined as having either: 1) fasting plasma glucose ≥ 126 mg/dl, 2) HbA1c ≥ 6.5%, 3) medication for hyperglycemia or 4) postprandial plasma glucose ≥ 200 mg/dl during the follow-up period. We measured serum FA levels and estimated the activity of ⊿5desaturase (D5D) by calculating the ratio of serum arachidonic acid to dihomo-γ-linolenic acid (DGLA) . The subjects were also divided into two groups by the cutoff point of waist circumference (WC) ≥ 90 cm. In multivariate analysis, the HR of developing diabetes was 2.81 [95%CI: 1.to 7.15, P=0.03] in the highest quartile of serum DGLA proportion and 0.28 [95%CI: 0.to 0.90, P=0.03] in the highest quartile of D5D, compared with their lowest quartiles, respectively. In stratified analysis, the multivariate adjusted risk of diabetes was higher in participants with low D5D/low WC (2.56 [0.96 to 6.82]) or high D5D/high WC (2.77 [0.68 to 11.32]) , and was significantly higher in participants with low D5D/high WC (6.30 [1.95 to 20.33, P=0.002]) than in participants with high D5D/low WC. Our findings suggest that the combination of increased serum DGLA proportion and attenuated D5D activity is a risk factor for the incidence of diabetes in male Japanese, especially in those with WC ≥ 90 cm. Thus, the significance of serum FA measurements in predicting T2D is suggested. Disclosure A.Hata: None. N.Aki: None. T.Ichihara: None. A.Tamura: None. T.Minagawa: None. Y.Kuwamura: None. M.Funaki: Board Member; Mechanogenic, Inc. Funding Grants-in-aid for research from Tokushima Prefecture Local Government

Inhibition of Δ-6 desaturase reduces fatty acid re-esterification in 3T3-L1 adipocytes independent of changes in n3-PUFA cellular content

Δ-6 desaturase (D6D) is a key enzyme in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFA). Evidence suggests that reduced D6D activity not only disrupts LC-PUFA production, but also impacts whole body lipid handling and body weight; however, the mechanisms remain largely unexplored. Therefore, we investigated the effect of D6D inhibition on the regulation of lipid accumulation in 3T3-L1 adipocytes with and without changes in n-3 PUFA content. 3T3-L1 cells were treated with a D6D inhibitor (SC-26196) in the presence or absence of α-linolenic acid (ALA) throughout differentiation. We found that D6D inhibition blocked the conversion of ALA to eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPAn-3) when ALA was supplemented, while no changes in n-3 PUFA content were observed in cells treated with the D6D inhibitor alone. D6D inhibited cells had reduced triacylglycerol (TAG) accumulation despite an EPA/DPA deficiency. In addition, analyses of cellular protein markers, as well as non-esterified fatty acids and glycerol release in medium, suggested an increase in lipolysis and a decrease in fatty acid re-esterification in D6D-inhibited cells, independent of n-3 PUFA changes. To provide further evidence, we treated cells with the D6D inhibitor in the presence or absence of EPA and compared them with ALA-treated cells. Although EPA further reduced TAG content, the reduced markers of fatty acid re-esterification were not affected by ALA or EPA. Collectively, this study provides new insight showing that D6D inhibition reduces TAG accumulation and fatty acid re-esterification in adipocytes independent of changes in n-3 PUFA cellular content.

Soy Consumption, but Not Dairy Consumption, Is Inversely Associated with Fatty Acid Desaturase Activity in Young Adults.

Past research using hepatic rat microsomes showed that soy protein suppressed delta-6 desaturase activity (D6D) compared to casein (a dairy protein). The effects of soy and dairy on desaturase pathway activity in humans remain poorly investigated. The objective of this analysis was to investigate the association between soy and dairy consumption with plasma fatty acids and estimate the desaturase pathway activity in a multiethnic Canadian population of young adults. We analyzed data from men (n = 319) and women (n = 764) previously collected for the Toronto Nutrigenomics and Health Study. Food frequency questionnaires and plasma fatty acids were assessed. Relationships between soy and dairy beverages and food consumption with estimated desaturase activities were assessed by regression models and by grouping participants according to beverage and food intake data. Weak inverse associations (p ≤ 0.05) were found between soy consumption and the overall desaturation pathway activity, specifically D6D activity. When participants were grouped based on soy and dairy consumption habits, omega-6 LC-PUFAs, as well as various estimates of the desaturase pathway activity, were significantly lower in individuals consuming soy (with or without dairy) compared to individuals consuming only fluid milk and dairy products. In conclusion, soy consumption, not dairy consumption, appears to suppress desaturase pathway activity.

Association between FADS1 rs174547 and levels of long-chain PUFA: a meta-analysis.

In the present study, we analysed the effects of SNP rs174547 (T/C) in the fatty acid desaturase 1 (FADS1) gene on long-chain PUFA levels. Four databases were searched to retrieve related literature with keywords such as fatty acid (FA), SNP, FADS1 and rs174547. A meta-analysis of the data was performed using Stata12.0 software, including summary statistics, test for heterogeneity, evaluation of publication bias, subgroup analysis and sensitivity analysis. The associations between rs174547 in FADS1 and seven types of FA, and Δ-5 (D5D) and Δ-6 fatty acid desaturase (D6D) activity were assessed based on the pooled results from eleven papers. A total of 3713 individuals (1529 TT and 2184 TC + CC) were included. The results demonstrated that minor C allele carriers of rs174547 had higher linoleic acid (LA; P<0·001) and α-linolenic acid (P=0·020) levels, lower γ-linolenic acid (GLA; P=0·001) and arachidonic acid (P=0·024) levels, and lower D5D (P=0·005) and D6D (P=0·004) activities than the TT genotype group. Stratification analysis showed that minor C allele carriers of rs174547 had higher LA and lower GLA levels and lower D6D activities in plasma (LA, P<0·001; GLA, P<0·001; D6D activity, P<0·001) samples and in Asian populations (LA, P<0·001; GLA, P=0·001; D6D activity, P=0·001) than the TT genotype group. In conclusion, minor C allele carriers of the SNP rs174547 were associated with decreased activity of D5D and D6D.

Desaturase Activity and the Risk of Type 2 Diabetes and Coronary Artery Disease: A Mendelian Randomization Study.

Estimated Δ5-desaturase (D5D) and Δ6-desaturase (D6D) are key enzymes in metabolism of polyunsaturated fatty acids (PUFA) and have been associated with cardiometabolic risk; however, causality needs to be clarified. We applied two-sample Mendelian randomization (MR) approach using a representative sub-cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam Study and public data from DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) and Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) genome-wide association studies (GWAS). Furthermore, we addressed confounding by linkage disequilibrium (LD) as all instruments from FADS1 (encoding D5D) are in LD with FADS2 (encoding D6D) variants. Our univariable MRs revealed risk-increasing total effects of both, D6D and D5D on type 2 diabetes (T2DM) risk; and risk-increasing total effect of D6D on risk of coronary artery disease (CAD). The multivariable MR approach could not unambiguously allocate a direct causal effect to either of the individual desaturases. Our results suggest that D6D is causally linked to cardiometabolic risk, which is likely due to downstream production of fatty acids and products resulting from high D6D activity. For D5D, we found indication for causal effects on T2DM and CAD, which could, however, still be confounded by LD.

1983-P: Dihomo-Gamma-Linolenic Acid and Estimated Delta-5-Desaturase Activity Are Associated with Obesity and Metabolic Components in Type 2 Diabetic Patients

Polyunsaturated fatty acid (PUFA) is an essential class of dietary fatty acids, because of the lack of endogenous enzymes for desaturation in humans. Previous research on n-3 PUFA has demonstrated several health benefits and antiatherogenic actions, but n-6 PUFA have not received much research attention. We investigated whether serum fatty acid composition, especially n-6 PUFAs and desaturase activity, is associated with obesity in type 2 diabetic patients. Subjects were 80 type 2 diabetic patients (age: 60.3±13.9 years) who had no EPA agent intake. They were divided into two groups: obese group (n=52) with a BMI more than 25 kg/m2 and non-obese group (n=28) with a BMI less than 25 kg/m2. Fatty acid levels in serum were measured using gas chromatography. The desaturase activity for n-6 PUFAs was calculated as the arachidonic acid/dihomo-gamma-linolenic acid (DGLA) ratio for Δ5 desaturase (D5D). The obese group revealed a higher saturated fatty acid (SFA) and DGLA levels than those in the non-obese group. No significant difference was observed in the serum n-3 PUFA levels between the two groups. The D5D index of the obese group was significantly lower than that of the non-obese group. Serum DGLA levels showed significant positive correlations with waist circumference, BMI, triglyceride, and hepatic AST and ALT levels. Moreover, SFA showed a significant positive correlation with BMI. The levels of D5D index showed a significant negative correlation with BMI. Increase in serum DGLA levels was related to the number of metabolic factors. These results suggest that type 2 diabetic patients with obesity had changes in their blood fatty acid profile, especially increased DGLA levels. The high levels of blood DGLA indicate downregulation of n-6 metabolism, probably caused by the decreased activity of D5D. The fat quality in the diet and changes in desaturase activity might contribute to the development of obesity. Disclosure M. Saito: None. M. Higa: None. T. Suzuki: None. M. Michishita: None. M. Hijikata: None. K. Yamashita: None. K. Ikehara: None. T. Ichijo: None.

Fatty acid profile and estimated desaturase activities in whole blood are associated with metabolic health

BackgroundThe aim was to investigate if fatty acid profile and estimated desaturase activities; stearoyl CoA-desaturase (SCD), delta-5-desaturase and delta-6-desaturase (D5D; D6D), differ between individuals with metabolically healthy (MH) and unhealthy (MU) phenotypes. We also explored these associations according to BMI categories.MethodsMen and women at moderately elevated risk of cardiovascular disease were included in this cross-sectional study (n = 321). If subjects met ≥4 out of 5 criteria (elevated triglycerides, total and LDL-cholesterol, HbA1c and low HDL-cholesterol), they were classified as MU (n = 52). If levels were within reference ranges for ≥3 of the same criteria, subjects were classified as MH (n = 150). Utilizing the entire population, a score ranging from 0 to 5 denoting the number of MU criteria met was computed. Estimated desaturase activities were calculated as product-to-precursor ratio of fatty acids in whole blood (SCD16 [16:1n7/16:0], SCD18 [18:1n9/18:0], D5D [18:3n6/18:2n6], D6D [20:4n6/20:3n6]).ResultsIndividuals with MH had lower estimated SCD16 and SCD18 activities, whereas estimated D6D activity was higher compared to MU. Similar, SCD16 and SCD18 increased, whereas D6D decreased with increasing criteria of MU. Trends were similar across BMI categories.ConclusionsThis study supports the notion of estimated desaturase activities as possible novel biomarkers of metabolic health irrespectively of BMI.

Oils' Impact on Comprehensive Fatty Acid Analysis and Their Metabolites in Rats.

Fatty acids, especially polyunsaturated, and their metabolites (eicosanoids) play many pivotal roles in human body, influencing various physiological and pathological processes. The aim of the study was to evaluate the effect of supplementation with edible oils diverse in terms of fatty acid composition on fatty acid contents, activities of converting their enzymes, and on lipoxygenase metabolites of arachidonic and linoleic acids (eicosanoids) in rat serum. Female Sprague-Dawley rats divided into seven groups were used in the study. Animals from six groups were fed one of oils daily (carotino oil, made up by combining of red palm oil and canola oil, linseed oil, olive oil, rice oil, sesame oil, or sunflower oil). One group received a standard diet only. Fatty acids were determined using gas chromatography with flame ionization detection. Eicosanoids—hydroxyeicosatetraenoic (HETE) and hydroxyoctadecadienoic acids (HODE) were extracted using a solid-phase extraction method and analyzed with HPLC. Vegetable oils given daily to rats caused significant changes in serum fatty acid profile and eicosanoid concentrations. Significant differences were also found in desaturases’ activity, with the linseed and olive oil supplemented groups characterized by the highest D6D and D5D activity. These findings may play a significant role in various pathological states.

Changes in behavior and fatty acid composition induced by long-term reduction in murine Δ6-desaturation activity

Polyunsaturated fatty acids (PUFAs), especially arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), play an important role in biological regulation. In our previous study using mice deficient in Δ6 desaturase (D6D), we reported that ARA is required for body growth, while DHA is necessary for functional development. In mammals, ARA and DHA are supplied directly or by synthesis from linoleic acid (LA) and α-linolenic acid (ALA). However, as desaturase enzyme activity is immature or low in newborns, and humans with minor alleles of the gene encoding desaturase, respectively, they require dietary supplementation with ARA and DHA. To investigate how the body reacts to a long-term reduction in fatty acid synthesis, we measured behavioral changes and fatty acid composition in mice heterozygous for the D6D null mutation with reduced D6D activity fed a diet containing only LA and ALA as PUFAs. During the growth-maturity period, heterozygous mice showed a slightly change in interest and curiosity compared with the wild-type group. ARA levels were decreased in the brain and liver in the heterozygous group, especially during the growth-maturity period, whereas DHA levels were decreased in the liver only in the old age period, suggesting that there are differences in the synthesis of and demand for ARA and DHA during life. For newborns, and humans with minor alleles with low desaturase activity, direct ARA intake is particularly important during the growth-maturity period, but they may need to be supplemented with DHA in the old age period. Further research is needed to determine the optimal intake and duration of these fatty acids.

Association Between Genetic Variants in FADS1-FADS2 and ELOVL2 and Obesity, Lipid Traits, and Fatty Acids in Tunisian Population.

The aim of this study was to determine whether genetic variants in FADS1/FADS2 and ELOVL2 are associated with overweight–obesity and body mass index (BMI) and to assess the association between these genetic variants and lipid profile and fatty acid levels. A total of 259 overweight–obese patients were compared to 369 healthy controls. FADS1, FADS2, and ELOVL2 genes were associated with BMI and overweight–obesity (P ≤ .001). In an additive model, the C allele in each of these variants was associated with a lower BMI: −1.18, −0.90, and −1.23 units, respectively. Higher amounts of total cholesterol, low-density lipoprotein cholesterol, total saturated fatty acids (lauric [12:0], myristic [C14:0], palmitic [C16:0], stearic [C18:0], arachidic [20:0], lignoceric [24:0]), monounsaturated fatty acids (myristoleic [C14:1], erucic [C22:1 n-9]), and polyunsaturated fatty acids (α-linolenic [ALA, 18:3 n-3], docosahexaenoic [DHA, C22:6 n-3], eicosapentaenoic acid [EPA, C20:5n-3], arachidonic acid [AA, 20:4n-6], and conjugated linolenic acids [CLA1 and CLA2]) were shown in patients. A significant increase in D6D activities presented by 20:4n-6/18:2n-6 and 18:3n-6/18:2n-6, Δ9 desaturase (D9D) activity, estimated by the ratio 18:1n-9/18:0 and elongase activities (AE), and estimated by the ratio of docosatetraenoic/AA and DPA/EPA in patients. The C minor allele of FADS1 had significantly lower DHA. A significant decrease in stearic acid, EPA, and AE activity (docosatetraenoic/AA) was revealed in patients with the minor allele carriers of FADS2. The C minor allele of ELOVL2 had significantly lower ALA, EPA, DPA, and D6D activity (C20:4 n-6/C18:2n-6). These data suggest that variations in FADS1, FADS2, and ELOVL2 affect the risk of overweight–obesity and the level of circulating fatty acids and could point to a key molecular pathway of metabolic syndrome and its related comorbidities.

A high-carbohydrate diet induces greater inflammation than a high-fat diet in mouse skeletal muscle.

We previously reported that both the high-carbohydrate diet (HCD) and high-fat diet (HFD) given for two months promote lipid deposition and inflammation in the liver and brain of mice. The results obtained indicate a tissue-specific response to both diets. Herein, we compared the effects of HCD and HFD on fatty acid (FA) composition and inflammation in the gastrocnemius muscle. Male Swiss mice were fed with HCD or HFD for 1 or 2 months. Saturated FA (SFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA), and n-6 PUFA were quantified. The activities of stearoyl-CoA desaturase 1 (SCD-1), Δ-6 desaturase (D6D), elongase 6, and de novo lipogenesis (DNL) were estimated. As for indicators of the inflammatory tissue state, we measured myeloperoxidase (MPO) activity and gene expression of F4/80, tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, and IL-10. The HCD led to a lower deposition of SFA, MUFA, n-3 PUFA, and n-6 PUFA compared to HFD. However, the HCD increased arachidonic acid levels, SFA/n-3 PUFA ratio, DNL, SCD-1, D6D, and MPO activities, and expression of IL-6, contrasting with the general idea that increased lipid deposition is associated with more intense inflammation. The HCD was more potent to induce skeletal muscle inflammation than the HFD, regardless of the lower lipid accumulation.

Serum Polyunsaturated Fatty Acids in Middle Childhood and Body Mass Index Change Through Adolescence

Background: Polyunsaturated fatty acids (PUFA) status in childhood may be associated with adiposity development. Objective: To assess associations of serum PUFA biomarkers in childhood with change in body mass index (BMI)-for-age Z scores (BMIZ) through adolescence. Methods: We quantified serum PUFA at ages 5 and 10 years among 418 children from Santiago, Chile. BMI was measured at 5, 10, and 16 years. We compared BMIZ change through age 16 years between quartiles of PUFA at 5 and 10 years and PUFA change 5–10 years by fitting growth curves from mixed effects models. Results: At age 5 years, serum docosahexaenoic acid was inversely associated with BMIZ change from ages 5 to 16 years. At age 10 years, arachidonic acid (AA) was nonlinearly positively related to BMIZ change from ages 10 to 16 years. Change in AA and the Δ5-desaturase (D5D) activity index between 5 and 10 years were each positively associated with BMIZ change from ages 10 to 16 years. Change in eicosapentaenoic acid was inversely associated with change in BMIZ. Conclusions: Serum long-chain n-3 PUFA in middle childhood were associated with less BMI gain through adolescence, whereas AA and D5D activity was related to greater BMI gain.

430-P: Plasma Delta-5 Desaturase Index Is Associated with Arterial Stiffness in Type 2 Diabetes

Decreased plasma n-3 polyunsaturated fatty acid (PUFA) levels or n-3/n-6 PUFA ratio is well known to be associated with the risk of cardiovascular diseases. The n-6 arachidonic acid (AA) to dihomo-γ-linolenic acid (DGLA) ratio in plasma, an indirect measure of delta-5 desaturase activity (D5D index), has been reported to be associated with insulin resistance, diabetes, and cardiovascular diseases. In this cross-sectional study, we investigated the association between plasma D5D index and arterial stiffness in patients with type 2 diabetes (T2D). This study included 382 patients with T2D and 118 healthy controls. Fasting plasma AA, DGLA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were measured by capillary gas chromatography. Arterial stiffness was assessed by measuring the heart-femoral pulse wave velocity (PWV). In patients with T2D, plasma AA levels (138.1 vs. 101.8 μg/mL, p&amp;lt;0.001) and plasma D5D index (5.85 vs. 4.49, p&amp;lt;0.001) were higher than the controls, while plasma DGLA levels were comparable to the controls (23.8 vs. 22.3 μg/mL, p=0.073). Patients with T2D had greater PWV than the controls (1141 vs. 935 cm/s, p&amp;lt;0.001). In the total population, the presence of T2D was independently associated with increased D5D index after adjusting for age, sex, and other metabolic parameters (β=0.311, p&amp;lt;0.001). Multivariate analysis in patients with T2D showed that D5D index was an independent determinant of PWV after adjusting for age, sex, (EPA+DHA)/AA ratio, and other cardiovascular risk factors (β=0.108, p=0.009). On the other hand, no significant association was found between D5D index and PWV in the controls. These data indicate that plasma n-6 AA/DGLA ratio, an estimate of D5D activity, is increased in patients with T2D and is associated with increased PWV, independently of classical cardiovascular risk factors and n-3 PUFAs. This study suggests that abnormal n-6 PUFA metabolism plays a role in advanced arterial stiffness in T2D. Disclosure T. Morioka: Research Support; Self; Eli Lilly and Company, Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Sanofi K.K., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk Inc., Roche Diagnostics K.K., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Other Relationship; Self; Ono Pharmaceutical Co., Ltd. M. Emoto: Research Support; Self; Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical CO., Ltd., Takeda Pharmaceutical Company Limited. Y. Kakutani: None. Y. Yamazaki: None. K. Mori: Speaker's Bureau; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd. S. Fukumoto: Research Support; Self; Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi K.K. A. Shioi: None. T. Shoji: Research Support; Self; Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd. Speaker's Bureau; Self; Kissei Pharmaceutical Co., Ltd., Kowa, Kyowa Hakko Kirin Co., Ltd. M. Inaba: None.

The Association of Polyunsaturated Fatty Acid δ-5-Desaturase Activity with Risk Factors for Type 2 Diabetes Is Dependent on Plasma ApoB-Lipoproteins in Overweight and Obese Adults

δ-5 and δ-6 desaturases (D5D and D6D) catalyze the endogenous conversion of n-3 (ω-3) and n-6 (ω-6) polyunsaturated fatty acids (PUFAs). Their activities are negatively and positively associated with type 2 diabetes (T2D), respectively, by unclear mechanisms. Elevated plasma apoB-lipoproteins (measured as plasma apoB), which can be reduced by n-3 PUFA intake, promote T2D risk factors. The aim of this study was to test the hypothesis that the association of D5D and D6D activities with T2D risk factors is dependent on plasma apoB. This is a pooled analysis of 2 populations recruited for 2 different metabolic studies. It is a post hoc analysis of baseline data of these subjects [n=98; 60% women (postmenopausal); mean ± SD body mass index (in kg/m2): 32.8±4.7; mean ± SD age: 57.6±6.3 y]. Glucose-induced insulin secretion (GIIS) and insulin sensitivity (IS) were measured using Botnia clamps. Plasma clearance of a high-fat meal (600 kcal/m2, 66% fat) and white adipose tissue (WAT) function (storage of 3H-triolein-labeled substrate) were assessed in a subpopulation (n=47). Desaturase activities were estimated from plasma phospholipid fatty acids. Associations were examined using Pearson and partial correlations. While both desaturase activities were positively associated with percentage of eicosapentaenoic acid, only D5D was negatively associated with plasma apoB (r=-0.30, P=0.003). Association of D5D activity with second-phase GIIS (r=-0.23, P=0.029), IS (r=0.33, P=0.015, in women) and 6-h area-under-the-curve (AUC6h) of plasma chylomicrons (apoB48, r=-0.47, P=0.020, in women) was independent of age and adiposity, but was eliminated after adjustment for plasma apoB. D6D activity was associated in the opposite direction with GIIS (r=0.24, P=0.049), IS (r=-0.36, P=0.004) and AUC6h chylomicrons (r=0.52, P=0.004), independent of plasma apoB. Both desaturases were associated with plasma interleukin-1-receptor antagonist (D5D: r=-0.45, P<0.001 in women; D6D: r=-0.33, P=0.007) and WAT function (trend for D5D: r=0.30, P=0.05; D6D: r=0.39, P=0.027) independent of any adjustment. Association of D5D activity with IS, lower GIIS, and plasma chylomicron clearance is dependent on plasma apoB in overweight and obese adults.

Adipose tissue polyunsaturated fatty acids and metabolic syndrome among adult parents and their children

Background and aimsPolyunsaturated fatty acids (PUFA) may play a role in the etiology of the metabolic syndrome (MetS). The aim of the study was to examine the associations of adipose tissue PUFA biomarkers with MetS among parents and children in Mesoamerica. Method and resultsWe conducted a cross-sectional study among 468 parents and 201 children aged 7–12 y from the capital cities of Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica, and Belize, and Tuxtla Gutiérrez in Mexico. We measured PUFA biomarkers in gluteal adipose tissue by gas chromatography. In adults, MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III definition. In children, we created an age- and sex-standardized metabolic risk score using abdominal circumference, the homeostasis model of insulin resistance, blood pressure, serum HDL cholesterol, and triglycerides. We estimated prevalence ratios of MetS and mean differences in metabolic score across quartiles of PUFA using multivariable-adjusted Poisson and linear regression models, respectively. Among adults, MetS was associated with low alpha-linolenic acid (ALA), high eicosapentaenoic acid (EPA), and low gamma-linolenic acid (GLA). It was linearly, positively associated with dihomo-gamma-linolenic acid (DGLA) and estimated Δ6-desaturase (D6D) activity. Among children, the metabolic score was positively associated with docosapentaenoic acid (DPA), DGLA, and D6D activity. ConclusionsAmong Mesoamerican adults, MetS prevalence is inversely associated with adipose tissue ALA and GLA, and positively associated with EPA, DGLA, and the D6D index. Among children, metabolic risk score is positively associated with DPA, DGLA, and the D6D index.

The type of dietary fat and dietary energy restriction affects the activity of the desaturases in the liver microsomes

The aim of present study was to investigate the effect of different dietary oils and the dietary energy restriction on the activity of enzymes participating in the process of arachidonic acid synthesis and on fatty acid profile in serum. It was also evaluated how diet modification affects the weight of animals and weight of the specific organs: liver, kidney and spleen. Wistar male rats were divided into 6 groups according to the diet fed (control, sunflower oil, olive oil, rapeseed oil, fish oil and a group of dietary energy restriction - DER group). The enzyme activities were established indirectly in liver microsomes. To this aim the method of high performance liquid chromatography with UV/VIS detection was used. In addition, the indices of ∆6-desaturase (D6D) and ∆5-desaturase (D5D) were determined. Significant differences in the concentrations of fatty acids and enzyme activity were observed. The results concerning desaturases show the negative correlation between n-3 polyunsaturated fatty acids intake and enzymes activity. The highest D6D activity was observed in microsomes obtained from sunflower oil fed rats and the lowest D6D activity was in the DER group. D5D index did not differ much depending on the diet. Among groups supplemented with oils the higher mean values of the weight of liver were observed in the group supplemented with rapeseed oil. Consumption of diets supplemented with edible oils of different fatty acid profile influence both serum fatty acid composition and the activity of ∆6- and Δ5-desaturase.