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Title: Docosahexaenoic acid and palmitic acid reciprocally modulate monocyte activation in part through endoplasmic reticulum stress

item SNODGRASS, RYAN - University Of California
item Huang, Shurong
item NAMGALADZE, DMITRY - Goethe University
item Jandali, Ola
item SHAO, TIFFANY - University Of California
item SAMA, SPANDANA - University Of California
item BRUNE, BERNHARD - Goethe University
item Hwang, Daniel

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/11/2015
Publication Date: 3/8/2016
Citation: Snodgrass, R.G., Huang, S., Namgaladze, D., Jandali, O., Shao, T., Sama, S., Brune, B., Hwang, D.H. 2016. Docosahexaenoic acid and palmitic acid reciprocally modulate monocyte activation in part through endoplasmic reticulum stress. Journal of Lipid Research. doi: 10.1016/j.jnutbio.2016.01.010.

Interpretive Summary: Pregnant women who are deficient in vitamin D may be at greater risk for certain adverse events in pregnancy, including elevated blood pressure, insulin resistance, and preeclampsia. The optimal level of vitamin D supplementation during pregnancy is currently unknown. In this study, we tested whether supplementation with 2,000 IU vitamin D per day compared to 400 IU per day was more effective at increasing maternal vitamin D status and protecting against adverse outcomes during pregnancy. Fifty-seven pregnant women in Sacramento and Davis, CA participated in this double-blind supplementation trial from mid-pregnancy (less than 20 weeks) until delivery. We found that the higher daily dose (2,000 IU per day) of supplemental vitamin D increased vitamin D levels in the blood to a greater extent than did the lower dose (400 IU per day). Women taking 2,000 IU per day had lower diastolic blood pressure at the end of pregnancy and delivered infants with greater birth weights compared to the women taking 400 IU per day. The higher dose of vitamin D also improved markers of immune function that are associated with decreased systemic inflammation in pregnancy. These data suggest that intake of 2,000 IU vitamin D per day during pregnancy may be beneficial for numerous outcomes for both mother and infant.

Technical Abstract: Background: Vitamin D deficiency is widespread in pregnancy and has been associated with adverse health conditions for mothers and infants. Vitamin D supplementation in pregnancy may support maintenance of pregnancy by its effects on innate immunity and T cell function. Objective: We assessed the effects of vitamin D supplementation during pregnancy on vitamin D status, inflammatory markers, and T cell numbers and cytokines. Design: We conducted a randomized, controlled, double-blind intervention of two doses of vitamin D (400 IU/d vs. 2,000 IU/d) from <20 weeks through delivery in fifty-seven pregnant women at risk for vitamin D deficiency in Sacramento and Davis, California. Vitamin D status was measured with LC/MS and T cell immune responses were assessed by flow cytometry. Results: Supplementation with 2,000 IU vitamin D per day had a greater effect on increasing 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D levels at mid- and late pregnancy than 400 IU. The percent IL-10+ CD4+ T cells and plasma levels of IL-1', IL-8, and TFG-' increased with vitamin D treatment. The percent IL-6+ CD4+ T cells and plasma TNF-' decreased with vitamin D treatment. Cytokine expression from stimulated innate cells and the plasma concentration of IL-6, TNF-' and neopterin increased with pregnancy progression. The proportion of IFN-'+ CD4+ and CD8+ T cells, IL-17+ CD4+ T cells, and FoxP3+ regulatory T cells and the concentration of T cell cytokines decreased with pregnancy progression. Conclusions: Supplementation with 2,000 IU/d is more effective at increasing vitamin D status in pregnant women than 400 IU/d and is associated with Th2-type and regulatory cell-mediated immunity and innate immunity, which promote regulation of maternal immune function during pregnancy and defense against infection, respectively. Further investigation is needed to determine the effects of supplementation on clinical outcomes such as maternal hypertension and infant birth weight.