Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury

Abstract The liver is an exclusive organ with tremendous regenerative capacity. Liver metabolic functions exhibit spatial heterogeneity, reflecting liver zonation. The mechanisms controlling the proliferation of hepatocytes and the accompanying matrix reconstruction during regeneration have been wel...

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Autores principales:	Atsushi Miura, Takashi Hosono, Taiichiro Seki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fb6f6eefdb6043e4a9cd608ab7d11bce
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spelling	oai:doaj.org-article:fb6f6eefdb6043e4a9cd608ab7d11bce2021-12-02T16:51:38ZMacrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury10.1038/s41598-021-88989-92045-2322https://doaj.org/article/fb6f6eefdb6043e4a9cd608ab7d11bce2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88989-9https://doaj.org/toc/2045-2322Abstract The liver is an exclusive organ with tremendous regenerative capacity. Liver metabolic functions exhibit spatial heterogeneity, reflecting liver zonation. The mechanisms controlling the proliferation of hepatocytes and the accompanying matrix reconstruction during regeneration have been well explored, but the recovery potential of differentiated metabolic functions and zonation after liver injury remains unclear. We employed a mouse model of carbon tetrachloride (CCl4) induced-acute liver injury with clodronate-induced macrophage depletion to clarify the impact of liver injury on liver metabolism and recovery dynamics of metabolic function and liver zonation during regeneration. Depleting macrophages suppressed tissue remodelling and partially delayed cell proliferation during regeneration after liver injury. In addition, recovery of metabolic functions was delayed by suppressing the tissue remodelling caused by the depleted macrophages. The model revealed that drug metabolic function was resilient against the dysfunction caused by liver injury, but glutamine synthesis was not. Metabolomic analysis revealed that liver branched-chain amino acid (BCAA) and carbohydrate metabolism were suppressed by injury. The plasma BCAA concentration reflected recovery of hepatic function during regeneration. Our study reveals one aspect of the regenerative machinery for hepatic metabolism following acute liver injury.Atsushi MiuraTakashi HosonoTaiichiro SekiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Atsushi Miura Takashi Hosono Taiichiro Seki Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury
description	Abstract The liver is an exclusive organ with tremendous regenerative capacity. Liver metabolic functions exhibit spatial heterogeneity, reflecting liver zonation. The mechanisms controlling the proliferation of hepatocytes and the accompanying matrix reconstruction during regeneration have been well explored, but the recovery potential of differentiated metabolic functions and zonation after liver injury remains unclear. We employed a mouse model of carbon tetrachloride (CCl4) induced-acute liver injury with clodronate-induced macrophage depletion to clarify the impact of liver injury on liver metabolism and recovery dynamics of metabolic function and liver zonation during regeneration. Depleting macrophages suppressed tissue remodelling and partially delayed cell proliferation during regeneration after liver injury. In addition, recovery of metabolic functions was delayed by suppressing the tissue remodelling caused by the depleted macrophages. The model revealed that drug metabolic function was resilient against the dysfunction caused by liver injury, but glutamine synthesis was not. Metabolomic analysis revealed that liver branched-chain amino acid (BCAA) and carbohydrate metabolism were suppressed by injury. The plasma BCAA concentration reflected recovery of hepatic function during regeneration. Our study reveals one aspect of the regenerative machinery for hepatic metabolism following acute liver injury.
format	article
author	Atsushi Miura Takashi Hosono Taiichiro Seki
author_facet	Atsushi Miura Takashi Hosono Taiichiro Seki
author_sort	Atsushi Miura
title	Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury
title_short	Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury
title_full	Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury
title_fullStr	Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury
title_full_unstemmed	Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury
title_sort	macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fb6f6eefdb6043e4a9cd608ab7d11bce
work_keys_str_mv	AT atsushimiura macrophagepotentiatestherecoveryofliverzonationandmetabolicfunctionafteracuteliverinjury AT takashihosono macrophagepotentiatestherecoveryofliverzonationandmetabolicfunctionafteracuteliverinjury AT taiichiroseki macrophagepotentiatestherecoveryofliverzonationandmetabolicfunctionafteracuteliverinjury
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Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury

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