Objective: Physical exercise and vitamin E are considered effective treatments of nonalcoholic fatty liver and other metabolic diseases. However, vitamin E has also been shown to interfere with the adaptation to exercise training, in particular for the skeletal muscle. Here, we studied the hypothesis that vitamin E also interferes with the metabolic adaptation of the liver to acute exercise. Methods: Male C57BL6/N mice were fed either control or vitamin E (α-tocopherol)- supplemented antioxidant diet during four weeks before being subjected to a non-exhaustive treadmill run. We assessed the acute transcriptional response of the liver as well as plasma corticosterone and free fatty acid (FFA) concentrations and monitored respiration in the exercising mice. Results: Vitamin E counteracted exercise-induced hepatic inflammation and altered the metabolic adaptation of the liver on the level of gene transcription. Vitamin E interfered with the upregulation of key metabolic regulators and caused a paradoxical increase in transcripts involved in lipid and cholesterol synthesis, processes negatively regulated by FFA and usually suspended during physical exercise. Whole-body energy consumption as well as corticosterone levels and signalling were similar, arguing against acute differences in fatty acid oxidation or glucocorticoid action. Conclusions: Our results show that vitamin E supplementation alters the inflammatory and transcriptional response of the liver to physical exercise. These effects of vitamin E could, on the long run, result in an impaired adaptation of the liver to physical exercise. Since exercise is clearly beneficial for general health and in reducing inflammation and dyslipidemia in nonalcoholic fatty liver disease, the interference of vitamin E with these processes may speak for a cautious use as dietary supplement.
Overall design
We performed gene expression microarray analysis on liver tissue derived from mice treated for four weeks with a vitamin E-enriched antioxidant diet prior to an acute non-exhaustive treadmill run and control mice.
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