Modulation of Cellular Biochemistry, Epigenetics and Metabolomics by Ketone Bodies. Implications of the Ketogenic Diet in the Physiology of the Organism and Pathological States.
Ketone bodies (KBs), comprising β-hydroxybutyrate, acetoacetate and acetone, are a set of fuel molecules serving as an alternative energy source to glucose. KBs are mainly produced by the liver from fatty acids during periods of fasting, and prolonged or intense physical activity. In diabetes, mainly type-1, ketoacidosis is the pathological response to glucose malabsorption. Endogenous production of ketone bodies is promoted by consumption of a ketogenic diet (KD), a diet virtually devoid of carbohydrates. Despite its recently widespread use, the systemic impact of KD is only partially understood, and ranges from physiologically beneficial outcomes in particular circumstances to potentially harmful effects. Here, we firstly review ketone body metabolism and molecular signaling, to then link the understanding of ketone bodies' biochemistry to controversies regarding their putative or proven medical benefits. We overview the physiological consequences of ketone bodies' consumption, focusing on (i) KB-induced histone post-translational modifications, particularly β-hydroxybutyrylation and acetylation, which appears to be the core epigenetic mechanisms of activity of β-hydroxybutyrate to modulate inflammation; (ii) inflammatory responses to a KD; (iii) proven benefits of the KD in the context of neuronal disease and cancer; and (iv) consequences of the KD's application on cardiovascular health and on physical performance.
['Dąbek|Arkadiusz|A|', 'Wojtala|Martyna|M|', 'Pirola|Luciano|L|', 'Balcerczyk|Aneta|A|']
D020155:3-Hydroxybutyric Acid D000090:Acetoacetates D000818:Animals D003922:Diabetes Mellitus, Type 1 D055423:Diet, Ketogenic D044127:Epigenesis, Genetic D057890:Epigenomics D006801:Humans D007657:Ketone Bodies D007662:Ketosis D055432:Metabolomics D009369:Neoplasms D009422:Nervous System Diseases
epigenetics ketone bodies ketogenic diet β-hydroxybutyrate inflammatory response cancer