Voluntary Wheel Running Reduces Hepatic Dendritic And Cytotoxic T Cells In Western Diet-fed C57Bl/6 J Mice

Abstract

The activation of innate immunity and recruitment of infiltrating macrophages are critical components of non-alcoholic steatohepatitis (NASH). In mice, voluntary wheel running (VWR) has improved hepatic steatosis and markers of inflammation; however, few studies have evaluated the effects of VWR on hepatic macrophages and hepatic immune cells linked to the development of NASH. PURPOSE: To determine the preventative effects of voluntary wheel running on hepatic macrophages and hepatic immune cells in mice fed a Western diet for 18 weeks. METHODS: Male, 8-week old, C57Bl/6 J mice (n = 56; 14/group) were randomly assigned to either a normal diet (ND) or Western diet (WD; 45% lard, 17% fructose, 0.75% cholesterol), followed by again randomly dividing each dietary group into either a sedentary (SED) or VWR group. Following 18-weeks, the relative percentage of hepatic macrophages (F4/80intCD11b+Ly6C- Kupffer cell, F4/80intCD11b+Ly6C+ infiltrating macrophage, and F4/80+CD11b+CD11c+ dendritic cell) and hepatic immune cells (CD45+CD19+ B-cell, CD45+CD4+ T-cell, and CD45+CD8+ cytotoxic T-cell) were isolated and cell populations were identified by flow cytometry. Differences between the four groups (ND + SED, ND + VWR, WD + SED, and WD + VWR) were identified by one-way ANOVA. RESULTS: No significant differences in either macrophage or immune cell populations were observed between ND + SED and ND + VWR. When compared to ND + SED, WD + SED had significantly (p < 0.05) higher percentage of cytotoxic T-cells (3.4 ± 0.5% vs. 8.2 ± 1.9%), dendritic cells (2.1 ± 0.4% vs. 8.6 ± 2.0%), and infiltrating macrophages (0.6 ± 0.5% vs. 1.6 ± 1.9%). In contrast, WD + VWR had lower percentages of cytotoxic T-cells (3.9 ± 0.5%) and dendritic cells (5.4 ± 1.1%) such that the percentage of cells were not significantly different than ND + SED and ND + VWR. Infiltrating macrophages remained relatively unchanged (1.4 ± 0.2%) in WD + VWR. Despite the positive changes in WD + VWR, the percentage of cytotoxic T-cells (p = 0.056) and dendritic cells (p = 0.387) were not significantly different than WD + SED mice. CONCLUSIONS: In mice fed a Western diet for 18 weeks, voluntary wheel running reduced the relative percentage of dendritic cells and cytotoxic T cells in the liver. Supported by SIUE Seed Grants for Transitional and Exploratory Projects.