In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease

The in situ metabolic profiling of the kidney is crucial to investigate the complex metabolic reprogramming underlying diabetic kidney disease (DKD) and to allow exploration of potential metabolic targets to improve kidney function. However, as the kidney is a highly heterogeneous organ, traditional...

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Autores principales:	Bai Linnan, Wang Yanzhe, Zhang Ling, Liu Yuyuan, Chen Sijia, Xie Xinmiao, Li Fengqin, Wang Xiaoxia
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	mass spectrometry imaging metabolomics diabetic kidney disease metabolic pathways metabolic reprogramming Physiology QP1-981
Acceso en línea:	https://doaj.org/article/378c65e7afa5459098cde860ba9ff152
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spelling	oai:doaj.org-article:378c65e7afa5459098cde860ba9ff1522021-12-01T20:23:09ZIn situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease1664-042X10.3389/fphys.2021.779683https://doaj.org/article/378c65e7afa5459098cde860ba9ff1522021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.779683/fullhttps://doaj.org/toc/1664-042XThe in situ metabolic profiling of the kidney is crucial to investigate the complex metabolic reprogramming underlying diabetic kidney disease (DKD) and to allow exploration of potential metabolic targets to improve kidney function. However, as the kidney is a highly heterogeneous organ, traditional metabolomic methods based on bulk analysis that produce an averaged measurement are inadequate. Herein, we employed an in situ metabolomics approach to discover alternations of DKD-associated metabolites and metabolic pathways. A series of histology-specific metabolic disturbances were discovered in situ using airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI–MSI). In combination with integrated metabolomics analysis, five dysfunctional metabolic pathways were identified and located in the kidneys of type-2 DKD mice simultaneously for the first time, including taurine metabolism, arginine and proline metabolism, histidine metabolism, biosynthesis of unsaturated fatty acids, and fatty acid degradation pathways. As crucial nodes of metabolic pathways, five dysregulated rate-limiting enzymes related to altered metabolic pathways were further identified. These findings reveal alternations from metabolites to enzymes at the molecular level in the progression of DKD and provide insights into DKD-associated metabolic reprogramming.Bai LinnanWang YanzheZhang LingLiu YuyuanChen SijiaXie XinmiaoLi FengqinWang XiaoxiaFrontiers Media S.A.articlemass spectrometry imagingmetabolomicsdiabetic kidney diseasemetabolic pathwaysmetabolic reprogrammingPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mass spectrometry imaging metabolomics diabetic kidney disease metabolic pathways metabolic reprogramming Physiology QP1-981
spellingShingle	mass spectrometry imaging metabolomics diabetic kidney disease metabolic pathways metabolic reprogramming Physiology QP1-981 Bai Linnan Wang Yanzhe Zhang Ling Liu Yuyuan Chen Sijia Xie Xinmiao Li Fengqin Wang Xiaoxia In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease
description	The in situ metabolic profiling of the kidney is crucial to investigate the complex metabolic reprogramming underlying diabetic kidney disease (DKD) and to allow exploration of potential metabolic targets to improve kidney function. However, as the kidney is a highly heterogeneous organ, traditional metabolomic methods based on bulk analysis that produce an averaged measurement are inadequate. Herein, we employed an in situ metabolomics approach to discover alternations of DKD-associated metabolites and metabolic pathways. A series of histology-specific metabolic disturbances were discovered in situ using airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI–MSI). In combination with integrated metabolomics analysis, five dysfunctional metabolic pathways were identified and located in the kidneys of type-2 DKD mice simultaneously for the first time, including taurine metabolism, arginine and proline metabolism, histidine metabolism, biosynthesis of unsaturated fatty acids, and fatty acid degradation pathways. As crucial nodes of metabolic pathways, five dysregulated rate-limiting enzymes related to altered metabolic pathways were further identified. These findings reveal alternations from metabolites to enzymes at the molecular level in the progression of DKD and provide insights into DKD-associated metabolic reprogramming.
format	article
author	Bai Linnan Wang Yanzhe Zhang Ling Liu Yuyuan Chen Sijia Xie Xinmiao Li Fengqin Wang Xiaoxia
author_facet	Bai Linnan Wang Yanzhe Zhang Ling Liu Yuyuan Chen Sijia Xie Xinmiao Li Fengqin Wang Xiaoxia
author_sort	Bai Linnan
title	In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease
title_short	In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease
title_full	In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease
title_fullStr	In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease
title_full_unstemmed	In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease
title_sort	in situ metabolomics of metabolic reprogramming involved in a mouse model of type 2 diabetic kidney disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/378c65e7afa5459098cde860ba9ff152
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In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease

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