Ketogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats

Abstract A better understanding of the secondary injury mechanisms that occur after traumatic spinal cord injury (SCI) is essential for the development of novel neuroprotective strategies linked to the restoration of metabolic deficits. We and others have shown that Ketogenic diet (KD), a high fat,...

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Autores principales:	Oscar Seira, Kathleen Kolehmainen, Jie Liu, Femke Streijger, Anne Haegert, Stéphane Lebihan, Robert Boushel, Wolfram Tetzlaff
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1f2733d484a0470f9d8ce5642cf37911
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spelling	oai:doaj.org-article:1f2733d484a0470f9d8ce5642cf379112021-12-02T18:50:57ZKetogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats10.1038/s41598-021-96003-52045-2322https://doaj.org/article/1f2733d484a0470f9d8ce5642cf379112021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96003-5https://doaj.org/toc/2045-2322Abstract A better understanding of the secondary injury mechanisms that occur after traumatic spinal cord injury (SCI) is essential for the development of novel neuroprotective strategies linked to the restoration of metabolic deficits. We and others have shown that Ketogenic diet (KD), a high fat, moderate in proteins and low in carbohydrates is neuroprotective and improves behavioural outcomes in rats with acute SCI. Ketones are alternative fuels for mitochondrial ATP generation, and can modulate signaling pathways via targeting specific receptors. Here, we demonstrate that ad libitum administration of KD for 7 days after SCI rescued mitochondrial respiratory capacity, increased parameters of mitochondrial biogenesis, affected the regulation of mitochondrial-related genes, and activated the NRF2-dependent antioxidant pathway. This study demonstrates that KD improves post-SCI metabolism by rescuing mitochondrial function and supports the potential of KD for treatment of acute SCI in humans.Oscar SeiraKathleen KolehmainenJie LiuFemke StreijgerAnne HaegertStéphane LebihanRobert BoushelWolfram TetzlaffNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Oscar Seira Kathleen Kolehmainen Jie Liu Femke Streijger Anne Haegert Stéphane Lebihan Robert Boushel Wolfram Tetzlaff Ketogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats
description	Abstract A better understanding of the secondary injury mechanisms that occur after traumatic spinal cord injury (SCI) is essential for the development of novel neuroprotective strategies linked to the restoration of metabolic deficits. We and others have shown that Ketogenic diet (KD), a high fat, moderate in proteins and low in carbohydrates is neuroprotective and improves behavioural outcomes in rats with acute SCI. Ketones are alternative fuels for mitochondrial ATP generation, and can modulate signaling pathways via targeting specific receptors. Here, we demonstrate that ad libitum administration of KD for 7 days after SCI rescued mitochondrial respiratory capacity, increased parameters of mitochondrial biogenesis, affected the regulation of mitochondrial-related genes, and activated the NRF2-dependent antioxidant pathway. This study demonstrates that KD improves post-SCI metabolism by rescuing mitochondrial function and supports the potential of KD for treatment of acute SCI in humans.
format	article
author	Oscar Seira Kathleen Kolehmainen Jie Liu Femke Streijger Anne Haegert Stéphane Lebihan Robert Boushel Wolfram Tetzlaff
author_facet	Oscar Seira Kathleen Kolehmainen Jie Liu Femke Streijger Anne Haegert Stéphane Lebihan Robert Boushel Wolfram Tetzlaff
author_sort	Oscar Seira
title	Ketogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats
title_short	Ketogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats
title_full	Ketogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats
title_fullStr	Ketogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats
title_full_unstemmed	Ketogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats
title_sort	ketogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1f2733d484a0470f9d8ce5642cf37911
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Ketogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats

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