Increased adipose tissue positively correlates with circulating inflammatory cytokines such as IL-6. We previously reported that adipose stem cells from genetically obese ob/ob mice produce significantly higher levels of IL-6 compared with other cell types such as adipocytes and macrophages within adipose tissue. We also demonstrated that (n-3) PUFA have antiinflammatory effects on adipocyte IL-6 secretion. Based on these findings, we hypothesized that EPA [20:5 (n-3)] and stearidonic acid [SDA, 18:4 (n-3)] would decrease LPS (200 μg/L)-induced IL-6 secretion and IL-6 mRNA content in the adipose stem cells. SDA (100 μmol/L) and EPA (100 μmol/L) significantly reduced LPS-induced IL-6 secretion and decreased IL-6 mRNA expression. To determine the underlying intracellular mechanisms, we tested whether LPS-induced Toll-like-receptor (TLR) 4 and TLR2 expression were modulated by these fatty acids using Western-blot analysis. EPA and SDA suppressed LPS-induced TLR2 but not TLR4 protein expression in the adipose stem cells. Furthermore, SDA and EPA significantly lowered the activation and translocation of NF-κB, a TLR2 downstream signaling target, while protein expression of extracellular signal-regulated kinases-1/2 were unaffected. Collectively, our results suggest that EPA and SDA inhibit LPS-induced IL-6 secretion and IL-6 mRNA expression in the adipose stem cells by decreasing TRL2-mediated signaling pathways.
Vitamin B6-restricted diets and low plasma pyridoxal 5′-phosphate (PLP) status altered plasma polyunsaturated fatty acids (PUFA) compositions. Evidence suggests the role of gender in the metabolism of vitamin B6 and PUFA. However, no epidemiologic study examined the impact of gender on the relationship between vitamin B6 and PUFA status in adults. Thus, we investigated whether there were gender differences in the association of vitamin B6 intake and plasma PLP concentration with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, (EPA + DHA)/AA) in US young/middle-aged adults. In total, 864 participants (20–59 years; 484 men, 380 women) from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 were used for this cross-sectional study. Nutrient intakes were estimated from two 24 h recalls and supplement questionnaires; plasma PLP and PUFA were measured. Multivariate linear regression was utilized to obtain unstandardized (b) and standardized (β) coefficients. Covariates included demographic, socioeconomic, dietary variables, physical activity level, cigarette smoking status, alcohol consumption, prescription medication use, and BMI. There were significant interactions between gender and PLP on EPA (P-interaction = 0.004), DHA (P-interaction = 0.020), EPA + DHA (P-interaction = 0.010), EPA/AA (P-interaction = 0.002), (EPA + DHA)/AA (P-interaction = 0.004), whereas no interaction between gender and B6 intake existed. In gender-stratified analyses, in men, PLP was positively associated with EPA (β = 0.138, b = 0.104, p = 0.0004), DHA (β = 0.101, b = 0.058, p = 0.036), EPA + DHA (β = 0.125, b = 0.073, p = 0.005), EPA/AA (β = 0.144, b = 0.099, p = 0.0002), (EPA + DHA)/AA (β = 0.123, b = 0.068, p = 0.005). However, no associations between PLP and PUFA existed in women. In conclusion, gender differences were found in the relationships between plasma PLP and plasma EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA, with significant direct associations in men only among US young/middle-aged adults.
Previous evidence suggests a potential dual impact of aging and vitamin B6 (B6) deficiency on polyunsaturated fatty acid (PUFA) metabolism; gender may influence PUFA biosynthesis. Perturbation of PUFA compositions during B6 deficiency could be linked to age-related health outcomes. However, little is known about the interrelationships between vitamin B6, PUFA, and gender in the older population. Therefore, we investigated whether gender-specific associations of B6 intake and plasma pyridoxal 5’-phosphate (PLP) concentration, respectively, with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA) existed in older adults. We further examined the relationships of adequate B6 status (PLP ≥ 20 nmol/L) with high (above median) plasma PUFA relative to deficient B6 status. This cross-sectional study analyzed 461 participants aged ≥60 years from NHANES 2003–2004. Nutrient intakes were assessed using two 24-h recalls and supplement questionnaires. PLP and PUFA concentrations were measured. Multivariate linear regression assessed the association of B6 intake and PLP with PUFA; multivariate logistic regression evaluated the relationship of adequate B6 status with high plasma PUFA, adjusting for demographic, socioeconomic, and dietary factors; physical activity; smoking; alcohol; medication; and BMI. There were interactions between gender and B6 intake on EPA (P-interaction = 0.008) and AA (P-interaction = 0.004) only, whereas no interaction existed between gender and PLP on PUFA. PLP was directly associated with EPA (β = 0.181, P = 0.002), DHA (β = 0.109, P = 0.005), EPA + DHA (β = 0.14, P = 0.002), EPA/AA (β = 0.186, P = 0.004), and (EPA + DHA)/AA (β = 0.13, P = 0.026). The odds of having high plasma EPA (adjusted (a) OR: 2.03, P = 0.049) and EPA/AA (aOR: 3.83, P < 0.0001) were greater in those with adequate B6 status compared to those with deficient B6 status. In conclusion, in US older adults, a higher PLP level was associated with a greater level of EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA. Adequate B6 status was associated with high EPA and EPA/AA status. These findings suggest that sufficient vitamin B6 status may positively influence PUFA metabolism in older adults.
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