Mechanism-Based Biomarker Prediction for Low-Grade Inflammation in Liver and Adipose Tissue

Metabolic disorders, such as obesity and type 2 diabetes have a large impact on global health, especially in industrialized countries. Tissue-specific chronic low-grade inflammation is a key contributor to complications in metabolic disorders. To support therapeutic approaches to these complications...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jolanda H. M. van Bilsen, Willem van den Brink, Anita M. van den Hoek, Remon Dulos, Martien P. M. Caspers, Robert Kleemann, Suzan Wopereis, Lars Verschuren
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	mechanism low-grade inflammation blood-based biomarker metabolic disease lifestyle intervention Physiology QP1-981
Acceso en línea:	https://doaj.org/article/3ea9afe3f4e84bb98f8daa842fd35854
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3ea9afe3f4e84bb98f8daa842fd35854
record_format	dspace
spelling	oai:doaj.org-article:3ea9afe3f4e84bb98f8daa842fd358542021-11-10T06:56:03ZMechanism-Based Biomarker Prediction for Low-Grade Inflammation in Liver and Adipose Tissue1664-042X10.3389/fphys.2021.703370https://doaj.org/article/3ea9afe3f4e84bb98f8daa842fd358542021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.703370/fullhttps://doaj.org/toc/1664-042XMetabolic disorders, such as obesity and type 2 diabetes have a large impact on global health, especially in industrialized countries. Tissue-specific chronic low-grade inflammation is a key contributor to complications in metabolic disorders. To support therapeutic approaches to these complications, it is crucial to gain a deeper understanding of the inflammatory dynamics and to monitor them on the individual level. To this end, blood-based biomarkers reflecting the tissue-specific inflammatory dynamics would be of great value. Here, we describe an in silico approach to select candidate biomarkers for tissue-specific inflammation by using a priori mechanistic knowledge from pathways and tissue-derived molecules. The workflow resulted in a list of candidate markers, in part consisting of literature confirmed biomarkers as well as a set of novel, more innovative biomarkers that reflect inflammation in the liver and adipose tissue. The first step of biomarker verification was on murine tissue gene-level by inducing hepatic inflammation and adipose tissue inflammation through a high-fat diet. Our data showed that in silico predicted hepatic markers had a strong correlation to hepatic inflammation in the absence of a relation to adipose tissue inflammation, while others had a strong correlation to adipose tissue inflammation in the absence of a relation to liver inflammation. Secondly, we evaluated the human translational value by performing a curation step in the literature using studies that describe the regulation of the markers in human, which identified 9 hepatic (such as Serum Amyloid A, Haptoglobin, and Interleukin 18 Binding Protein) and 2 adipose (Resistin and MMP-9) inflammatory biomarkers at the highest level of confirmation. Here, we identified and pre-clinically verified a set of in silico predicted biomarkers for liver and adipose tissue inflammation which can be of great value to study future development of therapeutic/lifestyle interventions to combat metabolic inflammatory complications.Jolanda H. M. van BilsenWillem van den BrinkAnita M. van den HoekRemon DulosMartien P. M. CaspersRobert KleemannSuzan WopereisLars VerschurenFrontiers Media S.A.articlemechanismlow-grade inflammationblood-based biomarkermetabolic diseaselifestyle interventionPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mechanism low-grade inflammation blood-based biomarker metabolic disease lifestyle intervention Physiology QP1-981
spellingShingle	mechanism low-grade inflammation blood-based biomarker metabolic disease lifestyle intervention Physiology QP1-981 Jolanda H. M. van Bilsen Willem van den Brink Anita M. van den Hoek Remon Dulos Martien P. M. Caspers Robert Kleemann Suzan Wopereis Lars Verschuren Mechanism-Based Biomarker Prediction for Low-Grade Inflammation in Liver and Adipose Tissue
description	Metabolic disorders, such as obesity and type 2 diabetes have a large impact on global health, especially in industrialized countries. Tissue-specific chronic low-grade inflammation is a key contributor to complications in metabolic disorders. To support therapeutic approaches to these complications, it is crucial to gain a deeper understanding of the inflammatory dynamics and to monitor them on the individual level. To this end, blood-based biomarkers reflecting the tissue-specific inflammatory dynamics would be of great value. Here, we describe an in silico approach to select candidate biomarkers for tissue-specific inflammation by using a priori mechanistic knowledge from pathways and tissue-derived molecules. The workflow resulted in a list of candidate markers, in part consisting of literature confirmed biomarkers as well as a set of novel, more innovative biomarkers that reflect inflammation in the liver and adipose tissue. The first step of biomarker verification was on murine tissue gene-level by inducing hepatic inflammation and adipose tissue inflammation through a high-fat diet. Our data showed that in silico predicted hepatic markers had a strong correlation to hepatic inflammation in the absence of a relation to adipose tissue inflammation, while others had a strong correlation to adipose tissue inflammation in the absence of a relation to liver inflammation. Secondly, we evaluated the human translational value by performing a curation step in the literature using studies that describe the regulation of the markers in human, which identified 9 hepatic (such as Serum Amyloid A, Haptoglobin, and Interleukin 18 Binding Protein) and 2 adipose (Resistin and MMP-9) inflammatory biomarkers at the highest level of confirmation. Here, we identified and pre-clinically verified a set of in silico predicted biomarkers for liver and adipose tissue inflammation which can be of great value to study future development of therapeutic/lifestyle interventions to combat metabolic inflammatory complications.
format	article
author	Jolanda H. M. van Bilsen Willem van den Brink Anita M. van den Hoek Remon Dulos Martien P. M. Caspers Robert Kleemann Suzan Wopereis Lars Verschuren
author_facet	Jolanda H. M. van Bilsen Willem van den Brink Anita M. van den Hoek Remon Dulos Martien P. M. Caspers Robert Kleemann Suzan Wopereis Lars Verschuren
author_sort	Jolanda H. M. van Bilsen
title	Mechanism-Based Biomarker Prediction for Low-Grade Inflammation in Liver and Adipose Tissue
title_short	Mechanism-Based Biomarker Prediction for Low-Grade Inflammation in Liver and Adipose Tissue
title_full	Mechanism-Based Biomarker Prediction for Low-Grade Inflammation in Liver and Adipose Tissue
title_fullStr	Mechanism-Based Biomarker Prediction for Low-Grade Inflammation in Liver and Adipose Tissue
title_full_unstemmed	Mechanism-Based Biomarker Prediction for Low-Grade Inflammation in Liver and Adipose Tissue
title_sort	mechanism-based biomarker prediction for low-grade inflammation in liver and adipose tissue
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3ea9afe3f4e84bb98f8daa842fd35854
work_keys_str_mv	AT jolandahmvanbilsen mechanismbasedbiomarkerpredictionforlowgradeinflammationinliverandadiposetissue AT willemvandenbrink mechanismbasedbiomarkerpredictionforlowgradeinflammationinliverandadiposetissue AT anitamvandenhoek mechanismbasedbiomarkerpredictionforlowgradeinflammationinliverandadiposetissue AT remondulos mechanismbasedbiomarkerpredictionforlowgradeinflammationinliverandadiposetissue AT martienpmcaspers mechanismbasedbiomarkerpredictionforlowgradeinflammationinliverandadiposetissue AT robertkleemann mechanismbasedbiomarkerpredictionforlowgradeinflammationinliverandadiposetissue AT suzanwopereis mechanismbasedbiomarkerpredictionforlowgradeinflammationinliverandadiposetissue AT larsverschuren mechanismbasedbiomarkerpredictionforlowgradeinflammationinliverandadiposetissue
_version_	1718440461187678208

Mechanism-Based Biomarker Prediction for Low-Grade Inflammation in Liver and Adipose Tissue

Ejemplares similares