Voluntary Wheel Running Attenuates Hepatic NF-κB And Phospho-NF-κB Expression In Western Diet Fed C57BL/6 J Mice

Western diets high in saturated fat combined with a sedentary lifestyle are associated with an increased risk for obesity-related liver diseases. Hepatic inflammation, characterized by activation of nuclear transcription factors such as nuclear factor-κB (NF-κB), underlies the development of chronic liver diseases. Exercise can reduce obesity-related inflammation; however, the effects of exercise on lowering the expression of NF-κB and its phosphorylated form (phospho-NF-κB) are unclear. PURPOSE: To determine the interaction of voluntary wheel running (VWR) and the consumption of a Western diet (WD) after 18 weeks on the hepatic expression of NF-κB and phospho-NF-κB in C57Bl/6 J mice. METHODS: Male C57Bl/6 J mice (n = 56) were randomly assigned at 8 weeks old into two diet groups: Western diet (WD; 45% kcal lard, 17% kcal fructose, 0.75% w/v cholesterol) or normal diet (ND; 10% kcal lard). Diet groups were then randomly assigned into either sedentary (SED) or VWR for a total of four groups (ND + SED, ND + VWR, WD + SED, and WD + VWR). Following 18 weeks, mice were sacrificed, and liver samples were collected. Tissues were homogenized and protein levels of NF-κB and phospho-NF-κB were assessed by Western blotting. Main effects and interactions of diet and activity were evaluated by a 2 x 2 (diet x activity) ANOVA with significance set at p < 0.05 level. RESULTS: A significant (p < 0.0001) diet effect was observed for body mass, where WD mice were heavier than ND mice (43.8 ± 0.8 g vs. 28.1 ± 0.8 g); however, no significant activity effect or diet x activity interaction was reported for body mass. A significant (p < 0.001) diet effect was observed for NF-κB expression, but not phospho-NF-κB (p = 0.127). A significant diet by activity interaction was observed for both NF-κB (p = 0.018) and phospho-NF-κB (p = 0.027). Post hoc tests revealed lower NF-κB levels in WD + VWR vs. WD + SED (0.79 ± 0.12 vs. 1.20 ± 0.12; p = 0.015). In addition, hepatic phospho-NF-κB was significantly lower in WD + VWR when compared to WD + SED (0.67 ± 0.16 vs. 1.17 ± 0.16; p = 0.028). CONCLUSIONS: Despite no difference in body mass between WD + SED and WD + VWR, exercise significantly lowered hepatic levels of NF-κB and phospho-NF-κB in C57Bl/6 J mice fed a WD compared to SED mice. These findings suggest that exercise may mitigate hepatic inflammation while concurrently consuming a WD.