(OR09-05-24) Dietary Vitamin A Deficiency in Rodents Impacts Oxylipin Metabolism and Gene Expression of Oxidative Enzymes

Objectives: Vitamin A and iron deficiencies are the most prevalent micronutrient deficiencies that commonly coexist in affected individuals, with pregnant women and children being the most vulnerable groups. The current study used a mouse model to investigate the role of vitamin A deficiency in modulating iron homeostasis and lipid metabolism, emphasizing oxylipin profiles.

Methods: C57/BL6J female mice were fed either a vitamin A-deficient (VDID) or a vitamin A-replete (VRID) low-iron (10 mg/kg) diet throughout two consecutive gestations (G1 and G2) and lactations. The offspring were fed the same diet as their dams from weaning to 6 (G2) or 9 weeks of age (G1 and G2).  Iron and hemoglobin were analyzed in all offspring subgroups, while oxylipins were determined in the brain, liver, and plasma of 9-week G1 mice.

Results: Oxylipin analysis showed lower arachidonic acid metabolites (P = 0.049) in the brain of VDID mice compared to VRID mice. Docosahexaenoic acid-derived oxylipins (P = 0.0338) were increased in VDID mice, while subsequent metabolites produced by soluble epoxy hydroxylase were downregulated compared to VRID. Alterations in oxylipin expression in the liver and plasma were also found. Hepatic CYP2J9 had greater expression in G1 VDID (N=3 per sex and treatment) mice (P= 0.0378) compared to G1 VRID (N=3-4 per sex and treatment) mice, while VRID had greater expression of RXR-alpha (P = 0.0443). While brain expression of ALOX5 was low, it had shown an upregulation (P= 0.0416) in G1 VDID mice compared to VRID mice. The various CYP oxidative enzymes had shown low/no expression in the brain.  Hepatic iron concentration did not differ between G1 at 9 weeks or G2 at 6 weeks of age. G2 9 weeks of age had a higher hepatic iron concentration in VDID mice than in VRID mice (P= 0.0005).

Conclusions: The first study showing vitamin A deficiency altered oxylipin metabolism in the brain and upregulated select oxidative enzymes in the brain and liver. Low brain expression of oxidative enzymes suggests a non-local production of oxylipins. Minimal influences of iron metabolism were detected in our rodent model.

Funding Sources: NIFA Hatch/Multistate Funding