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The effect of FADS2 gene rs174583 polymorphism on desaturase activities, fatty acid profile, insulin resistance, biochemical indices, and incidence of type 2 diabetes.

ABSTRACT: Background:In this study, we investigated the associations of erythrocytes fatty acid composition, activities of delta-5 desaturase (D5D) and delta-6 desaturase (D6D), and other metabolic risk factors, with type 2 diabetes (T2D) risk to determine if rs174583 polymorphism of FADS2 gene had any effect on these associations. Materials and Methods:Fatty acid profile of erythrocytes was determined using gas chromatography-mass spectrometry in 95 T2D patients and 95 apparently healthy participants. The genotypes of single-nucleotide polymorphism (SNP) of FADS2 gene were determined using the polymerase chain reaction-restriction fragment length polymorphism technique. Other biochemical parameters were measured in the serum using standard analytical procedures. Results:D6D activity was increased (P < 0.001) and D5D activity was decreased in T2D patients (P < 0.001) compared to controls. Homeostatic model assessment insulin resistance (HOMA-IR) index was positively correlated with D6D (r = 0.34, P < 0.001) and negatively correlated with D5D (r = -0.19, P = 0.02). Palmitic acid (P < 0.001) and dihomo-gamma-linolenic acid (P = 0.03) were higher and linoleic acid (P < 0.001) and arachidonic acid (AA) (P < 0.001) were lower in T2D patients. The distribution of rs174583 genotypes which includes C/T, C/C, and T/T was not different in the two groups (P = 0.63). Conclusion:In the population studied, there was a strong association in the erythrocytes fatty acid composition, D5D and D6D activities and other metabolic risk factors between non-T2D and T2D patients. In addition, there was a strong association in erythrocytes DGLA and AA contents and D5D activities between rs174583 genotypes in all participants. However, the distribution of rs174583 genotypes did not differ significantly between T2D patient and controls, and it did not appear to be an association between rs174583 SNP and incident of T2D.

SUBMITTER: Mazoochian L

PROVIDER: S-EPMC5996566 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The effect of FADS2 gene rs174583 polymorphism on desaturase activities, fatty acid profile, insulin resistance, biochemical indices, and incidence of type 2 diabetes.

Mazoochian Leila L Mohammad Sadeghi Hamid Mir HM Pourfarzam Morteza M

Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences 20180530

<h4>Background</h4>In this study, we investigated the associations of erythrocytes fatty acid composition, activities of delta-5 desaturase (D5D) and delta-6 desaturase (D6D), and other metabolic risk factors, with type 2 diabetes (T2D) risk to determine if rs174583 polymorphism of FADS2 gene had any effect on these associations.<h4>Materials and methods</h4>Fatty acid profile of erythrocytes was determined using gas chromatography-mass spectrometry in 95 T2D patients and 95 apparently healthy p ...[more]

PMID: 29937909

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Project description:BackgroundRecent studies have shown that dietary intakes and gene variants have a critical role in the obesity related comorbidities. This study aimed to evaluate the effects of the interactions between Fatty acid desaturase 2 (FADS2) gene rs174583 polymorphism and two dietary indices on cardiometabolic risk factors.MethodsThis cross-sectional study was carried out on 347 obese adults aged 20-50 years old in Tabriz, Iran. Healthy eating index (HEI) and Diet quality index-international (DQI-I) were evaluated by a validated semi-quantitative 147-item Food frequency questionnaire (FFQ). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine FADS2 gene variants. Multivariate analysis of covariance (MANCOVA) was used to identify gene-diet interactions on metabolic parameters.ResultsWaist circumference (WC) and serum triglyceride (TG) levels were significantly higher among carriers of TT genotype of FADS2 gene (P < 0.05). In addition, the interactions between FADS2 gene rs174583 polymorphism and DQI-I had significant effects on weight (P interaction = 0.01), fat mass (P interaction = 0.04), fat free mass (P interaction = 0.03), and Body mass index (BMI) (P interaction = 0.02); the highest level of these parameters belonged to TT carriers. Similarly, the interactions between FADS2 gene variants and HEI had significant effects on insulin (P interaction < 0.001), Homeostasis model assessment of insulin resistance (HOMA-IR) (P interaction < 0.001), Quantitative insulin check index (QUICKI) (P interaction = 0.001), and alpha Melanocyte stimulating hormone (α-MSH) (P interaction = 0.03).ConclusionIn this study, for the first time, we reported the effects of gene-diet interactions on metabolic traits. Compliance with dietary indices (DQI-I and HEI) ameliorated the adverse effects of gene variants on metabolic risk factors, especially in heterogeneous genotypes. Further prospective cohort studies are needed to confirm these results.

Project description:Background and Aim: Genetic variation in fatty acid desaturases (FADS) has previously been linked to several diet-related diseases. We aimed to determine whether the FADS2 rs174583 variant interacts with the Dietary Approach to Stop Hypertension (DASH) score and Mediterranean dietary score (MDS) to influence cardio-metabolic risk factors among obese adults. Methods: This cross-sectional study was performed among 347 apparently healthy obese adults (aged 20-50 years). Dietary quality indicator scores (DASH and MDS) were generated using a validated 147-item Food Frequency Questionnaire (FFQ). The FADS2 rs174583 variant was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The gene-diet interaction was analyzed by the ANCOVA multivariate interaction model. Results: A significant interaction was observed between rs174583 and adherence to the DASH score in relation to serum triglyceride (TG) concentration among the female group (P Interaction = 0.046); CT-genotype carriers who were assigned to the second tertile of DASH compared with those in the first tertile had a lower TG level (P < 0.05). Another significant interaction was revealed between adherence to MDS score and rs174583 polymorphism on serum glucose levels (P Interaction = 0.044); the lowest mean of glucose level was observed in homozygous minor subjects (TT) in the third tertile of MDS, in comparison with other tertiles of this dietary index (P < 0.05). There was a similar significant interaction between DASH and rs174583 in relation to diastolic blood pressure (P Interaction = 0.038) among the male group. Additionally, a significant positive association was found between TT genotype and odds of having high TG both in the crude (OR, 3.21; 95% CI, 1.02-10.14) and adjusted (OR, 3.58; 95% CI, 1.07-11.97) models, taking into account different confounders. Conclusion: Adherence to the dietary quality indicators (DASH and MDS) modified the relationship between FADS2 rs174583 polymorphism and cardio-metabolic risk factors in obese subjects. Prospective cohort studies are needed to confirm the results of our study.

Project description:Polyunsaturated fatty acids (PUFAs) are essential dietary components. They are not only used for energy, but also act as signaling molecules. The delta-6 desaturase (D6D) enzyme, encoded by the FADS2 gene, is one of two rate limiting enzymes that convert the PUFA precursors - α-linolenic (n-3) and linoleic acid (n-6) to their respective metabolites. Alterations in the D6D enzyme activity alters fatty acid profiles and are associated with metabolic and inflammatory diseases including cardiovascular disease and type 2 diabetes. Omega-3 PUFAs, specifically its constituent fatty acids DHA and EPA, are known for their anti-inflammatory ability and are also beneficial in the prevention of skeletal muscle wasting, however the mechanism for muscle preservation is not well understood. Moreover, little is known of the effects of altering the n-6/n-3 ratio in the context of a high-fat diet, which is known to downregulate protein synthesis. Twenty C57BL6 male mice were fed a high-fat lard (HFL, 45% fat (mostly lard), 35% carbohydrate and 20% protein, n-6:n-3 PUFA, 13:1) diet for 6 weeks. Mice were then divided into 4 groups (n = 5 per group): HFL- , high-fat oil- (HFO, 45% fat (mostly Menhaden oil), 35% carbohydrate and 20% protein, n-6:n-3 PUFA, 1:3), HFL+ (HFL diet plus an orally administered FADS2 inhibitor, 100 mg/kg/day), and HFO+ (HFO diet plus an orally administered FADS2 inhibitor, 100 mg/kg/day). After 2 weeks on their respective diets and treatments, animals were sacrificed and gastrocnemius muscle harvested. Protein turnover signaling were analyzed via Western Blot. 4-EBP1 and ribosomal protein S6 expression were measured. A two-way ANOVA revealed no significant change in the phosphorylation of both 4EBP-1 and ribosomal protein S6 with diet or inhibitor. There was a significant reduction in STAT3 phosphorylation with the inhibition of FADS2 (p = 0.03). Additionally, we measured markers of protein degradation through levels of FOXO phosphorylation, ubiquitin, and LC3B expression; there was a trend towards increased phosphorylation of FOXO (p = 0.08) and ubiquitinated proteins (p = 0.05) with FADS2 inhibition. LC3B expression, a marker of autophagy, was significantly higher in the HFL plus FADS2 inhibition group from all other comparisons. Lastly, we analyzed activation of mitochondrial biogenesis which is closely linked with protein synthesis through PGC1-α and Cytochrome-C expression, however no significant differences were associated with either marker across all groups. Collectively, these data suggest that the protective effects of muscle mass by omega-3 fatty acids are from inhibition of protein degradation. Our aim was to determine the role of PUFA metabolites, DHA and EPA, in skeletal muscle protein turnover and assess the effects of n-3s independently. We observed that by inhibiting the FADS2 enzyme, the protective effect of n-3s on protein synthesis and proliferation was lost; concomitantly, protein degradation was increased with FADS2 inhibition regardless of diet.

Dataset Information

The effect of FADS2 gene rs174583 polymorphism on desaturase activities, fatty acid profile, insulin resistance, biochemical indices, and incidence of type 2 diabetes.

Publications

The effect of FADS2 gene rs174583 polymorphism on desaturase activities, fatty acid profile, insulin resistance, biochemical indices, and incidence of type 2 diabetes.

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