Acetyl-CoA derived from hepatic mitochondrial fatty acid β-oxidation aggravates inflammation by enhancing p65 acetylation

Summary: Acetylation coordinates many biological processes to ensure cells respond appropriately to nutrients. However, how acetylation regulates lipid surplus-induced inflammation remains poorly understood. Here, we found that a high-fat diet (HFD) enhanced mitochondrial fatty acid β-oxidation, whi...

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Autores principales:	Qiang Chen, Jianlong Du, Kun Cui, Wei Fang, Zengqi Zhao, Qiuchi Chen, Kangsen Mai, Qinghui Ai
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Pathophysiology Cellular physiology Immunology Science Q
Acceso en línea:	https://doaj.org/article/58a50713eb7c4de4b0905def7ddb8dbc
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spelling	oai:doaj.org-article:58a50713eb7c4de4b0905def7ddb8dbc2021-11-20T05:08:48ZAcetyl-CoA derived from hepatic mitochondrial fatty acid β-oxidation aggravates inflammation by enhancing p65 acetylation2589-004210.1016/j.isci.2021.103244https://doaj.org/article/58a50713eb7c4de4b0905def7ddb8dbc2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012128https://doaj.org/toc/2589-0042Summary: Acetylation coordinates many biological processes to ensure cells respond appropriately to nutrients. However, how acetylation regulates lipid surplus-induced inflammation remains poorly understood. Here, we found that a high-fat diet (HFD) enhanced mitochondrial fatty acid β-oxidation, which enhanced acetyl-CoA levels in the liver of the large yellow croaker. The HFD activated ACLY to govern the “citrate transport” to transfer acetyl-CoA from the mitochondria to the nucleus. Elevated acetyl-CoA activated CBP to increase p65 acetylation and then aggravated inflammation. SIRT1 was deactivated with a decline in NAD+/NADH, which further aggravated inflammation. Therefore, acetylation-dependent regulation of transcription factor activity is an adaptation to proinflammatory stimuli under nutrient stress, which was also confirmed in AML12 hepatocytes. In vitro octanoate stimulation further verified that acetyl-CoA derived from fatty acid β-oxidation mediated acetylation homeostasis in the nucleus. The broad therapeutic prospects of intermediate metabolites and acetyltransferases/deacetylases might provide critical insights for the treatment of metabolic diseases in vertebrates.Qiang ChenJianlong DuKun CuiWei FangZengqi ZhaoQiuchi ChenKangsen MaiQinghui AiElsevierarticlePathophysiologyCellular physiologyImmunologyScienceQENiScience, Vol 24, Iss 11, Pp 103244- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathophysiology Cellular physiology Immunology Science Q
spellingShingle	Pathophysiology Cellular physiology Immunology Science Q Qiang Chen Jianlong Du Kun Cui Wei Fang Zengqi Zhao Qiuchi Chen Kangsen Mai Qinghui Ai Acetyl-CoA derived from hepatic mitochondrial fatty acid β-oxidation aggravates inflammation by enhancing p65 acetylation
description	Summary: Acetylation coordinates many biological processes to ensure cells respond appropriately to nutrients. However, how acetylation regulates lipid surplus-induced inflammation remains poorly understood. Here, we found that a high-fat diet (HFD) enhanced mitochondrial fatty acid β-oxidation, which enhanced acetyl-CoA levels in the liver of the large yellow croaker. The HFD activated ACLY to govern the “citrate transport” to transfer acetyl-CoA from the mitochondria to the nucleus. Elevated acetyl-CoA activated CBP to increase p65 acetylation and then aggravated inflammation. SIRT1 was deactivated with a decline in NAD+/NADH, which further aggravated inflammation. Therefore, acetylation-dependent regulation of transcription factor activity is an adaptation to proinflammatory stimuli under nutrient stress, which was also confirmed in AML12 hepatocytes. In vitro octanoate stimulation further verified that acetyl-CoA derived from fatty acid β-oxidation mediated acetylation homeostasis in the nucleus. The broad therapeutic prospects of intermediate metabolites and acetyltransferases/deacetylases might provide critical insights for the treatment of metabolic diseases in vertebrates.
format	article
author	Qiang Chen Jianlong Du Kun Cui Wei Fang Zengqi Zhao Qiuchi Chen Kangsen Mai Qinghui Ai
author_facet	Qiang Chen Jianlong Du Kun Cui Wei Fang Zengqi Zhao Qiuchi Chen Kangsen Mai Qinghui Ai
author_sort	Qiang Chen
title	Acetyl-CoA derived from hepatic mitochondrial fatty acid β-oxidation aggravates inflammation by enhancing p65 acetylation
title_short	Acetyl-CoA derived from hepatic mitochondrial fatty acid β-oxidation aggravates inflammation by enhancing p65 acetylation
title_full	Acetyl-CoA derived from hepatic mitochondrial fatty acid β-oxidation aggravates inflammation by enhancing p65 acetylation
title_fullStr	Acetyl-CoA derived from hepatic mitochondrial fatty acid β-oxidation aggravates inflammation by enhancing p65 acetylation
title_full_unstemmed	Acetyl-CoA derived from hepatic mitochondrial fatty acid β-oxidation aggravates inflammation by enhancing p65 acetylation
title_sort	acetyl-coa derived from hepatic mitochondrial fatty acid β-oxidation aggravates inflammation by enhancing p65 acetylation
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/58a50713eb7c4de4b0905def7ddb8dbc
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Acetyl-CoA derived from hepatic mitochondrial fatty acid β-oxidation aggravates inflammation by enhancing p65 acetylation

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