The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line

The ketogenic diet (KD), a diet high in fat and protein but low in carbohydrates, is gaining much interest due to its positive effects, especially in neurodegenerative diseases. Beta-hydroxybutyrate (BHB), the major ketone body produced during the carbohydrate deprivation that occurs in KD, is assum...

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Main Authors: Rita Polito, Maria Ester La Torre, Fiorenzo Moscatelli, Giuseppe Cibelli, Anna Valenzano, Maria Antonietta Panaro, Marcellino Monda, Antonietta Messina, Vincenzo Monda, Daniela Pisanelli, Francesco Sessa, Giovanni Messina, Chiara Porro
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/4/3102
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author Rita Polito
Maria Ester La Torre
Fiorenzo Moscatelli
Giuseppe Cibelli
Anna Valenzano
Maria Antonietta Panaro
Marcellino Monda
Antonietta Messina
Vincenzo Monda
Daniela Pisanelli
Francesco Sessa
Giovanni Messina
Chiara Porro
author_facet Rita Polito
Maria Ester La Torre
Fiorenzo Moscatelli
Giuseppe Cibelli
Anna Valenzano
Maria Antonietta Panaro
Marcellino Monda
Antonietta Messina
Vincenzo Monda
Daniela Pisanelli
Francesco Sessa
Giovanni Messina
Chiara Porro
author_sort Rita Polito
collection DOAJ
description The ketogenic diet (KD), a diet high in fat and protein but low in carbohydrates, is gaining much interest due to its positive effects, especially in neurodegenerative diseases. Beta-hydroxybutyrate (BHB), the major ketone body produced during the carbohydrate deprivation that occurs in KD, is assumed to have neuroprotective effects, although the molecular mechanisms responsible for these effects are still unclear. Microglial cell activation plays a key role in the development of neurodegenerative diseases, resulting in the production of several proinflammatory secondary metabolites. The following study aimed to investigate the mechanisms by which BHB determines the activation processes of BV2 microglial cells, such as polarization, cell migration and expression of pro- and anti-inflammatory cytokines, in the absence or in the presence of lipopolysaccharide (LPS) as a proinflammatory stimulus. The results showed that BHB has a neuroprotective effect in BV2 cells, inducing both microglial polarization towards an M2 anti-inflammatory phenotype and reducing migratory capacity following LPS stimulation. Furthermore, BHB significantly reduced expression levels of the proinflammatory cytokine IL-17 and increased levels of the anti-inflammatory cytokine IL-10. From this study, it can be concluded that BHB, and consequently the KD, has a fundamental role in neuroprotection and prevention in neurodegenerative diseases, presenting new therapeutic targets.
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spelling doaj.art-5005d0ab564548cfb22e40b5e66d65482023-11-16T20:55:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244310210.3390/ijms24043102The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell LineRita Polito0Maria Ester La Torre1Fiorenzo Moscatelli2Giuseppe Cibelli3Anna Valenzano4Maria Antonietta Panaro5Marcellino Monda6Antonietta Messina7Vincenzo Monda8Daniela Pisanelli9Francesco Sessa10Giovanni Messina11Chiara Porro12Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalySection of Human Physiology and Unit of Dietetics and Sports Medicine, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalySection of Human Physiology and Unit of Dietetics and Sports Medicine, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalySection of Human Physiology and Unit of Dietetics and Sports Medicine, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, 95131 Catania, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyThe ketogenic diet (KD), a diet high in fat and protein but low in carbohydrates, is gaining much interest due to its positive effects, especially in neurodegenerative diseases. Beta-hydroxybutyrate (BHB), the major ketone body produced during the carbohydrate deprivation that occurs in KD, is assumed to have neuroprotective effects, although the molecular mechanisms responsible for these effects are still unclear. Microglial cell activation plays a key role in the development of neurodegenerative diseases, resulting in the production of several proinflammatory secondary metabolites. The following study aimed to investigate the mechanisms by which BHB determines the activation processes of BV2 microglial cells, such as polarization, cell migration and expression of pro- and anti-inflammatory cytokines, in the absence or in the presence of lipopolysaccharide (LPS) as a proinflammatory stimulus. The results showed that BHB has a neuroprotective effect in BV2 cells, inducing both microglial polarization towards an M2 anti-inflammatory phenotype and reducing migratory capacity following LPS stimulation. Furthermore, BHB significantly reduced expression levels of the proinflammatory cytokine IL-17 and increased levels of the anti-inflammatory cytokine IL-10. From this study, it can be concluded that BHB, and consequently the KD, has a fundamental role in neuroprotection and prevention in neurodegenerative diseases, presenting new therapeutic targets.https://www.mdpi.com/1422-0067/24/4/3102beta-hydroxybutyrate (BHB)microglial cell line (BV2)neuroinflammationneuroprotectionketogenic diet
spellingShingle Rita Polito
Maria Ester La Torre
Fiorenzo Moscatelli
Giuseppe Cibelli
Anna Valenzano
Maria Antonietta Panaro
Marcellino Monda
Antonietta Messina
Vincenzo Monda
Daniela Pisanelli
Francesco Sessa
Giovanni Messina
Chiara Porro
The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line
International Journal of Molecular Sciences
beta-hydroxybutyrate (BHB)
microglial cell line (BV2)
neuroinflammation
neuroprotection
ketogenic diet
title The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line
title_full The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line
title_fullStr The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line
title_full_unstemmed The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line
title_short The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line
title_sort ketogenic diet and neuroinflammation the action of beta hydroxybutyrate in a microglial cell line
topic beta-hydroxybutyrate (BHB)
microglial cell line (BV2)
neuroinflammation
neuroprotection
ketogenic diet
url https://www.mdpi.com/1422-0067/24/4/3102
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