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Molecular Mechanisms for Ketone Body Metabolism, Signaling Functions, and Therapeutic Potential in Cancer

The ketone bodies (KBs) β-hydroxybutyrate and acetoacetate are important alternative energy sources for glucose during nutrient deprivation. KBs synthesized by hepatic ketogenesis are catabolized to acetyl-CoA through ketolysis in extrahepatic tissues, followed by the tricarboxylic acid cycle and el...

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Autores principales: Hwang, Chi Yeon, Choe, Wonchae, Yoon, Kyung-Sik, Ha, Joohun, Kim, Sung Soo, Yeo, Eui-Ju, Kang, Insug
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694619/
https://www.ncbi.nlm.nih.gov/pubmed/36432618
http://dx.doi.org/10.3390/nu14224932
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author Hwang, Chi Yeon
Choe, Wonchae
Yoon, Kyung-Sik
Ha, Joohun
Kim, Sung Soo
Yeo, Eui-Ju
Kang, Insug
author_facet Hwang, Chi Yeon
Choe, Wonchae
Yoon, Kyung-Sik
Ha, Joohun
Kim, Sung Soo
Yeo, Eui-Ju
Kang, Insug
author_sort Hwang, Chi Yeon
collection PubMed
description The ketone bodies (KBs) β-hydroxybutyrate and acetoacetate are important alternative energy sources for glucose during nutrient deprivation. KBs synthesized by hepatic ketogenesis are catabolized to acetyl-CoA through ketolysis in extrahepatic tissues, followed by the tricarboxylic acid cycle and electron transport chain for ATP production. Ketogenesis and ketolysis are regulated by the key rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA synthase 2 and succinyl-CoA:3-oxoacid-CoA transferase, respectively. KBs participate in various cellular processes as signaling molecules. KBs bind to G protein-coupled receptors. The most abundant KB, β-hydroxybutyrate, regulates gene expression and other cellular functions by inducing post-translational modifications. KBs protect tissues by regulating inflammation and oxidative stress. Recently, interest in KBs has been increasing due to their potential for treatment of various diseases such as neurological and cardiovascular diseases and cancer. Cancer cells reprogram their metabolism to maintain rapid cell growth and proliferation. Dysregulation of KB metabolism also plays a role in tumorigenesis in various types of cancer. Targeting metabolic changes through dietary interventions, including fasting and ketogenic diets, has shown beneficial effects in cancer therapy. Here, we review current knowledge of the molecular mechanisms involved in the regulation of KB metabolism and cellular signaling functions, and the therapeutic potential of KBs and ketogenic diets in cancer.
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spelling pubmed-96946192022-11-26 Molecular Mechanisms for Ketone Body Metabolism, Signaling Functions, and Therapeutic Potential in Cancer Hwang, Chi Yeon Choe, Wonchae Yoon, Kyung-Sik Ha, Joohun Kim, Sung Soo Yeo, Eui-Ju Kang, Insug Nutrients Review The ketone bodies (KBs) β-hydroxybutyrate and acetoacetate are important alternative energy sources for glucose during nutrient deprivation. KBs synthesized by hepatic ketogenesis are catabolized to acetyl-CoA through ketolysis in extrahepatic tissues, followed by the tricarboxylic acid cycle and electron transport chain for ATP production. Ketogenesis and ketolysis are regulated by the key rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA synthase 2 and succinyl-CoA:3-oxoacid-CoA transferase, respectively. KBs participate in various cellular processes as signaling molecules. KBs bind to G protein-coupled receptors. The most abundant KB, β-hydroxybutyrate, regulates gene expression and other cellular functions by inducing post-translational modifications. KBs protect tissues by regulating inflammation and oxidative stress. Recently, interest in KBs has been increasing due to their potential for treatment of various diseases such as neurological and cardiovascular diseases and cancer. Cancer cells reprogram their metabolism to maintain rapid cell growth and proliferation. Dysregulation of KB metabolism also plays a role in tumorigenesis in various types of cancer. Targeting metabolic changes through dietary interventions, including fasting and ketogenic diets, has shown beneficial effects in cancer therapy. Here, we review current knowledge of the molecular mechanisms involved in the regulation of KB metabolism and cellular signaling functions, and the therapeutic potential of KBs and ketogenic diets in cancer. MDPI 2022-11-21 /pmc/articles/PMC9694619/ /pubmed/36432618 http://dx.doi.org/10.3390/nu14224932 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hwang, Chi Yeon
Choe, Wonchae
Yoon, Kyung-Sik
Ha, Joohun
Kim, Sung Soo
Yeo, Eui-Ju
Kang, Insug
Molecular Mechanisms for Ketone Body Metabolism, Signaling Functions, and Therapeutic Potential in Cancer
title Molecular Mechanisms for Ketone Body Metabolism, Signaling Functions, and Therapeutic Potential in Cancer
title_full Molecular Mechanisms for Ketone Body Metabolism, Signaling Functions, and Therapeutic Potential in Cancer
title_fullStr Molecular Mechanisms for Ketone Body Metabolism, Signaling Functions, and Therapeutic Potential in Cancer
title_full_unstemmed Molecular Mechanisms for Ketone Body Metabolism, Signaling Functions, and Therapeutic Potential in Cancer
title_short Molecular Mechanisms for Ketone Body Metabolism, Signaling Functions, and Therapeutic Potential in Cancer
title_sort molecular mechanisms for ketone body metabolism, signaling functions, and therapeutic potential in cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694619/
https://www.ncbi.nlm.nih.gov/pubmed/36432618
http://dx.doi.org/10.3390/nu14224932
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