Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching

Abstract Obesity increases susceptibility to multiple organ disorders, however, underlying mechanisms remain unclear. The subclinical inflammation assisted by obesity-induced gut permeability may underlie obesity-associated co-morbidities. Despite eminent clinical significance of the obesity led gut...

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Autores principales:	Rizwan Ahmad, Bilal Rah, Dhundy Bastola, Punita Dhawan, Amar B. Singh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fc524b4d98014de49588d878b953d7a5
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spelling	oai:doaj.org-article:fc524b4d98014de49588d878b953d7a52021-12-02T12:30:44ZObesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching10.1038/s41598-017-04989-82045-2322https://doaj.org/article/fc524b4d98014de49588d878b953d7a52017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04989-8https://doaj.org/toc/2045-2322Abstract Obesity increases susceptibility to multiple organ disorders, however, underlying mechanisms remain unclear. The subclinical inflammation assisted by obesity-induced gut permeability may underlie obesity-associated co-morbidities. Despite eminent clinical significance of the obesity led gut barrier abnormalities, its precise molecular regulation remains unclear. It is also unknown whether barrier deregulations, similar to the gut, characterize other vital organs in obese individuals. The claudin family of proteins is integral to the tight junction (TJ), the apical cell-cell adhesion and a key regulator of the epithelial barrier. Using comprehensive physiological and biochemical analysis of intestinal and renal tissues from high-fat diet fed mice, critical for maintaining metabolic homeostasis, this study demonstrates that profound TJ-restructuring by organ and tissue-specific claudin switching characterize obese organs. Protein expression and cellular distribution were examined. In-silico analysis further highlighted potential association of select claudins, modulated by the obesity, with signaling and metabolic pathways of pathological significance. In vitro studies using Leptin or DCA-treatment suggested causal significance of obesity-induced changes in tissue microenvironment in regulating barrier deregulations in tissue-specific manner. Overall, current findings advances our understanding of the molecular undertakings of obesity associated changes that help predispose to specific diseases and also identifies novel windows of preventive and/or therapeutic interventions.Rizwan AhmadBilal RahDhundy BastolaPunita DhawanAmar B. SinghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rizwan Ahmad Bilal Rah Dhundy Bastola Punita Dhawan Amar B. Singh Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching
description	Abstract Obesity increases susceptibility to multiple organ disorders, however, underlying mechanisms remain unclear. The subclinical inflammation assisted by obesity-induced gut permeability may underlie obesity-associated co-morbidities. Despite eminent clinical significance of the obesity led gut barrier abnormalities, its precise molecular regulation remains unclear. It is also unknown whether barrier deregulations, similar to the gut, characterize other vital organs in obese individuals. The claudin family of proteins is integral to the tight junction (TJ), the apical cell-cell adhesion and a key regulator of the epithelial barrier. Using comprehensive physiological and biochemical analysis of intestinal and renal tissues from high-fat diet fed mice, critical for maintaining metabolic homeostasis, this study demonstrates that profound TJ-restructuring by organ and tissue-specific claudin switching characterize obese organs. Protein expression and cellular distribution were examined. In-silico analysis further highlighted potential association of select claudins, modulated by the obesity, with signaling and metabolic pathways of pathological significance. In vitro studies using Leptin or DCA-treatment suggested causal significance of obesity-induced changes in tissue microenvironment in regulating barrier deregulations in tissue-specific manner. Overall, current findings advances our understanding of the molecular undertakings of obesity associated changes that help predispose to specific diseases and also identifies novel windows of preventive and/or therapeutic interventions.
format	article
author	Rizwan Ahmad Bilal Rah Dhundy Bastola Punita Dhawan Amar B. Singh
author_facet	Rizwan Ahmad Bilal Rah Dhundy Bastola Punita Dhawan Amar B. Singh
author_sort	Rizwan Ahmad
title	Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching
title_short	Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching
title_full	Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching
title_fullStr	Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching
title_full_unstemmed	Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching
title_sort	obesity-induces organ and tissue specific tight junction restructuring and barrier deregulation by claudin switching
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fc524b4d98014de49588d878b953d7a5
work_keys_str_mv	AT rizwanahmad obesityinducesorganandtissuespecifictightjunctionrestructuringandbarrierderegulationbyclaudinswitching AT bilalrah obesityinducesorganandtissuespecifictightjunctionrestructuringandbarrierderegulationbyclaudinswitching AT dhundybastola obesityinducesorganandtissuespecifictightjunctionrestructuringandbarrierderegulationbyclaudinswitching AT punitadhawan obesityinducesorganandtissuespecifictightjunctionrestructuringandbarrierderegulationbyclaudinswitching AT amarbsingh obesityinducesorganandtissuespecifictightjunctionrestructuringandbarrierderegulationbyclaudinswitching
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Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching

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