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The Interaction Between Fatty Acid Desaturase-2 (FADS2) rs174583 Genetic Variant and Dietary Quality Indices (DASH and MDS) Constructs Different Metabolic Phenotypes Among Obese Individuals.

ABSTRACT: 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.

SUBMITTER: Khodarahmi M

PROVIDER: S-EPMC8215104 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and aimThe association with obesity of a common variant near the melanocortin-4 receptor (MC4R) gene (rs17782313) has been indicated in various studies. Adherence to dietary quality indices also have shown to have potential favorable effects on obesity-related health outcomes. However, no study has examined the interaction between rs17782313 and the Dietary Approach to Stop Hypertension (DASH) score and the Mediterranean Dietary Score (MDS) on cardio-metabolic risk factors and hypothalamic hormones. Therefore, the purpose of the current study was to examine whether adherence to these dietary quality indices modifies the association of the MC4R rs17782313 polymorphism with cardio-metabolic risk factors and hypothalamic hormones among obese adults.MethodTwo hundred eighty-eight healthy obese adults were recruited in this cross-sectional study. Diet quality indices, including DASH score and MDS, were calculated from a validated 147-item food frequency questionnaire (FFQ). MC4R s17782313 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An ANCOVA multivariate interaction model was used to assess the gene-diet interaction.ResultsSignificant interactions were detected between DASH score and MC4R rs17782313 genotypes on systolic blood pressure (SBP), atherogenic index of plasma (AIP), and serum glucose and triglyceride (TG) among the female group (pInteraction < 0.05). In the male group, there were gene-DASH and gene-MDS interactions in relation to serum glucose concentration and plasma α-melanocyte stimulating hormone (MSH) levels, but these were found only in multi-adjusted interaction models (pInteraction < 0.05). In addition, there was a significant interaction between MC4R rs17782313 polymorphism and DASH score on plasma agouti-related peptide (AgRP) concentrations in the female group in a multivariate interaction model (pInteraction < 0.05). An inverse association between DASH score and chance of having the CC genotype in a multivariate-adjusted model among women was also revealed.ConclusionMC4R rs17782313 interacts with healthy dietary pattern (DASH score and MDS) to influence cardio-metabolic risk factors and hypothalamic hormones in obese individuals. Prospective cohort studies are needed to further assess these findings.

Project description:ObjectivePolymorphisms of the fatty acid desaturase (FADS) gene cluster have been associated with obesity and its-related consequences. This cross-sectional study aimed to investigate whether the adherence to dietary non-enzymatic antioxidant capacity (NEAC), reflecting the antioxidant potential of the whole diet, modifies the association of FADS2 rs174583 polymorphism with cardio-metabolic risk factors in obese adults.MethodsThe present study included 347 healthy obese adults (aged 20-50 years). Dietary NEAC was assessed by a validated food frequency questionnaire with 147 items and estimated through total radical-trapping antioxidant parameters (TRAP), oxygen radical absorbance capacity (ORAC), and ferric reducing ability of plasma (FRAP) with the use of published databases. FADS2 rs174583 polymorphism was characterized using PCR-RFLP. ANCOVA multivariate interaction model was used to analyze gene-diet interactions.Resultsafter adjustment for the confounding variables (age, physical activity, SES and WC), this study showed significant interactions between rs174583 polymorphism and adherence to dietary ORAC on the serum cholesterol (P Interaction = 0.029), LDL-C (P Interaction = 0.025) and HDL-C levels (P Interaction = 0.049) among the male group; minor allele carriers who had the highest adherence to the NEAC (ORAC) showed a better metabolic profile (lower TG and LDL-C and higher HDL-C) (P < 0.05). Among women, the dietary ORAC-rs174583 interactions were statistically significant for the serum insulin concentration (P Interaction = 0.020), QUICKI (P Interaction = 0.023) and HOMA-IR (P Interaction = 0.017); the highest QUICKI and the lowest HOMA-IR and serum insulin levels were observed in the CC homozygote carriers with the moderate compliance with the dietary ORAC (P < 0.05). In addition, the dietary TRAP modified the association between FADS2 variant and change in LDL-C levels (P Interaction = 0.037); the homozygous wild-type (CC) women who placed in the top tertile of TRAP had significantly the lowest LDL-C levels than those in the second tertile (P < 0.05).ConclusionThese data indicate that the FADS2 rs174583 polymorphism interacts with the dietary NEAC to influence cardio-metabolic risk factors in obese subjects. Replication in prospective cohort studies among other populations is required 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.

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The Interaction Between Fatty Acid Desaturase-2 (FADS2) rs174583 Genetic Variant and Dietary Quality Indices (DASH and MDS) Constructs Different Metabolic Phenotypes Among Obese Individuals.

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