Metabolic Responses in Endothelial Cells Following Exposure to Ketone Bodies.

Erika Meroni,Luca Massaccesi,Nicoletta Basilico,Daniela Erba,Franca Criscuoli,Nadia Papini,Maria C Casiraghi

doi:10.3390/nu10020250

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.

Highlights

One of the dietary approaches that has attracted particular success in recent years is the “ketogenic diet” (KD)
These results suggest that ketone bodies (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
The low glucose supply stimulates the catabolism of fats to obtain energy, leading to the accumulation of acetyl-CoA and synthesis of KB by the liver, which are sent to the peripheral tissues where they are oxidized to produce energy [8,9,10]

Summary

Introduction

One of the dietary approaches that has attracted particular success in recent years is the “ketogenic diet” (KD). This is a dietary program that was designed in the 1920s as a therapy for drug-resistant epilepsy [1,2], which gained popularity in the 1970s as a weight-loss diet (Atkins) [3,4]. The KD is a high-fat, low carbohydrates diet planned to achieve a metabolic state called ketosis, characterized by increased levels of circulating ketone bodies (KB), i.e., the compounds acetoacetate (AA), β-hydroxybutyrate (βHB) and acetone. Under normal conditions and with a balanced diet, KB are produced in small quantities, but, under a KD, their synthesis is induced as a result of a very low carbohydrate intake (VLCKD) and high fat intake. The low glucose supply stimulates the catabolism of fats to obtain energy, leading to the accumulation of acetyl-CoA and synthesis of KB by the liver, which are sent to the peripheral tissues where they are oxidized to produce energy [8,9,10]

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Conclusion