Metabolic Responses in Endothelial Cells Following Exposure to Ketone Bodies

Nutrients
Erika MeroniDaniela Erba

Abstract

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet based on the induction of the synthesis of ketone bodies (KB). Despite its widespread use, the systemic impact of KD is not completely understood. The purpose of this study was to evaluate the effects of physiological levels of KB on HMEC-1 endothelial cells. To this aim, DNA oxidative damage and the activation of Nrf2, a known transcriptional factor involved in cell responses to oxidative stress, were assessed. The exposure of cells to KB exerted a moderate genotoxic effect, measured by a significant increase in DNA oxidative damage. However, cells pre-treated with KB for 48 h and subjected to a secondary oxidative insult (H₂O₂), significantly decreased DNA damage compared to control oxidized cells. This protection occurred by the activation of Nrf2 pathway. In KB-treated cells, we found increased levels of Nrf2 in nuclear extracts and higher gene expression of HO-1, a target gene of Nrf2, compared to control cells. These results suggest that KB, by inducing moderate oxidative stress, activate the transcription factor Nrf2, which induces the transcription of target genes involved in the cellular antioxidant defense system.

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Citations

Jun 28, 2019·International Journal of Molecular Sciences·Silvia VidaliRené Günther Feichtinger
Oct 17, 2020·Oxidative Medicine and Cellular Longevity·Andy W C ManNing Xia
Mar 6, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Edward J Calabrese, Walter J Kozumbo

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Methods Mentioned

BETA
electrophoresis
PCR
scraping
nuclear translocation

Software Mentioned

iQ5
Pro Plus
SPSS Statistics
Image

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