(P11-030-23) α-Tocopherol Depletion Affects Lipopolysaccharide-Induced Muscle Weakness

Objectives: Immune cells contain higher vitamin E (α-tocopherol, αT) concentrations than other cell-types, and vitamin E deficiency (VED) has been shown to impair immune and brain function in rodents. However, in our prior 4-week vitamin E depletion study using αT transfer protein null (Ttpa^-/-) mice, VED did not significantly affect the lipopolysaccharide (LPS)-induced acute inflammatory and immune response. αT depletion can be more readily achieved in Ttpa^-/- mice than wild-type mice by feeding them an αT deficient diet. Thus, the Ttpa^-/- mouse model is a useful tool for studying the role of αT. Our objective was to assess whether a longer αT depletion phase alters the LPS-induced acute inflammatory response in the brain and muscle strength.

Methods: Male Ttpa^+/+ and Ttpa^-/- weanling littermates (n=12-14/genotype) were fed αT deficient diet ad libitum for 9 weeks. Ttpa^+/+ and Ttpa^-/- mice were then injected with LPS (10 µg/mouse) or saline (control) intraperitoneally and sacrificed 4 hours later. Concentrations of αT in diet and tissues were measured by HPLC. Cerebellar and serum IL-6 levels were measured via ELISA. Hippocampal Il-6 expression was measured by RT-qPCR. Muscle strength was measured via a grip strength meter apparatus 1 day before and 3.5 hours after LPS injection.

Results: αT concentrations in the liver, heart, and adipose tissue of Ttpa^+/+ mice were higher than Ttpa^-/- mice (P < 0.0001). αT was not detected in Ttpa^-/- mouse brain or serum. Hippocampal Il-6 expression and cerebellar and serum IL-6 protein levels were increased in LPS treated groups (P < 0.05). Muscle strength tended to be reduced in LPS-injected Ttpa^+/+ (P = 0.07), an effect that was significant in Ttpa^-/- mice (P < 0.0001). In a secondary analysis using a Student’s T-test, Ttpa^-/- mice had lower muscle strength than Ttpa^+/+ mice (P = 0.04).

Conclusions: Systemic LPS administration caused an acute inflammatory response with concomitant decline in muscle strength, especially in Ttpa^-/- mice. αT depletion appears to exacerbate neuromuscular dysfunction brought on by systemic inflammation.

Funding Sources: Abbott Nutrition via the Center for Nutrition, Learning and Memory, University of Illinois, Urbana-Champaign; Division of Nutritional Sciences (DNS) Vision 20/20 Grant Program; DNS Margin of Excellence Research Program.