(P17-026-24) Lipopolysaccharide-Induced Inflammatory Response Differs Over Time in Mice Fed an Alpha-Tocopherol Deficient Diet for 12 Weeks

Objectives: Vitamin E deficiency has detrimental effects on neurological and immune function. α-tocopherol (αT) is the most bioactive form of vitamin E, and mice lacking the αT transfer protein (Ttpa^-/-) are unable to transfer hepatic αT to other tissues, which makes them useful for modeling deficiency. We previously showed that lipopolysaccharide (LPS) injection following 9 weeks of αT depletion resulted in an acute inflammatory response and reduced grip strength 4 hours post-injection, especially in Ttpa^-/- mice. This study sought to evaluate a longer period of αT depletion and its effect on the capacity for recovery from LPS injection.

Methods: Male wild-type (WT) and Ttpa^-/- weanling littermates (n=50-68/genotype) were fed an αT deficient diet ad libitum for 12 weeks. Mice were injected intraperitoneally with 10 µg of LPS or saline (control) and sacrificed 4- or 24-hours post-injection. αT in tissues was measured by HPLC. Grip strength was measured 2 days before and 4- or 24-hours after injection. Inflammatory and oxidative stress response-related gene expression was assessed using RT-qPCR.

Results: Concentrations of αT in the brain, arm muscle, and liver of Ttpa^-/- mice were lower than WT mice at both time points. LPS treatment reduced hepatic αT accumulation 24 hours after injection. Grip strength was decreased in LPS-treated groups at 4 hours post-injection, but after 24 hours, mice recovered to baseline. Hippocampal Il6 and Ccl2 expression was increased 4 hours post-LPS injection, and Ccl2 remained elevated after 24 hours. LPS-treated groups had decreased hepatic expression of Gsr, Sod, and Cyp3a11, and increased Ccl2 expression 24-hours post-injection.

Conclusions: LPS administration induced an inflammatory response and sickness behavior, with some effects being maintained 24 hours after injection, particularly in the liver. LPS-treated mice had lower hepatic αT and suppressed expression of oxidative stress-related markers, suggesting that LPS injection may limit the recovery ability of mice fed an αT deficient diet, although differences were not seen between genotypes.

Funding Sources: Abbott Nutrition via the Center for Nutrition, Learning, and Memory, University of Illinois; Division of Nutritional Sciences Vision 20/20 and Margin of Excellence Research Program at the University of Illinois