Increased expression levels of PIEZO1 in visceral adipose tissue in obesity and type 2 diabetes are triggered by mechanical forces and are associated with inflammation

Abstract Background PIEZO1 has emerged as a mechanoreceptor linked with adipogenesis, adipose tissue (AT) inflammation and insulin resistance. We aimed to determine the impact of obesity and obesity-associated type 2 diabetes (T2D) as well as mechanical compression forces on the expression of PIEZO1...

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Main Authors: Victoria Catalán, Javier Gómez-Ambrosi, Beatriz Ramírez, Xabier Unamuno, Sara Becerril, Amaia Rodríguez, Jorge Baixauli, Gabriel Reina, Ana Sancho, Camilo Silva, Javier A. Cienfuegos, Gema Frühbeck
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Molecular Medicine
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Online Access:https://doi.org/10.1186/s10020-024-01008-1
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author Victoria Catalán
Javier Gómez-Ambrosi
Beatriz Ramírez
Xabier Unamuno
Sara Becerril
Amaia Rodríguez
Jorge Baixauli
Gabriel Reina
Ana Sancho
Camilo Silva
Javier A. Cienfuegos
Gema Frühbeck
author_facet Victoria Catalán
Javier Gómez-Ambrosi
Beatriz Ramírez
Xabier Unamuno
Sara Becerril
Amaia Rodríguez
Jorge Baixauli
Gabriel Reina
Ana Sancho
Camilo Silva
Javier A. Cienfuegos
Gema Frühbeck
author_sort Victoria Catalán
collection DOAJ
description Abstract Background PIEZO1 has emerged as a mechanoreceptor linked with adipogenesis, adipose tissue (AT) inflammation and insulin resistance. We aimed to determine the impact of obesity and obesity-associated type 2 diabetes (T2D) as well as mechanical compression forces on the expression of PIEZO1 in visceral AT (VAT) and its relation with inflammation. Methods Blood and VAT samples were obtained from 100 volunteers. Static compression studies in VAT explants were performed to study the PIEZO1 response. The effect of bariatric surgery on the expression of Piezo1 was assessed in a rat model of diet-induced obesity. Results Obesity and obesity-associated T2D increased (P < 0.01) gene expression levels of PIEZO1 in VAT mainly due to adipocytes. SWELL1 and key markers of inflammation (NLRP3, NLRP6, IL1B, IL18 and IL8) were also upregulated in VAT in obesity and T2D being significantly associated (P < 0.01) with PIEZO1 levels. We further showed that the static compression of VAT explants promoted an upregulation of PIEZO1 (P < 0.01) and SWELL1 (P < 0.01) expression levels together with a strong increase in the expression and release of key inflammatory mediators. The treatment of THP-1-derived macrophages with the secretome of adipocytes from patients with obesity upregulated (P < 0.001) PIEZO1 levels. Rats undergoing bariatric surgery exhibited decreased (P < 0.01) expression levels of Piezo1 in the epididymal AT. Conclusions Static compression triggered an upregulation of PIEZO1 in VAT explants together with a strong inflammation. In addition, the increased expression of PIEZO1 in VAT in obesity and obesity-associated T2D, primarily attributable to adipocytes, is closely associated with SWELL1 and inflammatory markers.
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spelling doaj-art-c15c66e79f4f4e6e81a624d7423c21012024-12-22T12:32:26ZengBMCMolecular Medicine1528-36582024-12-0130111510.1186/s10020-024-01008-1Increased expression levels of PIEZO1 in visceral adipose tissue in obesity and type 2 diabetes are triggered by mechanical forces and are associated with inflammationVictoria Catalán0Javier Gómez-Ambrosi1Beatriz Ramírez2Xabier Unamuno3Sara Becerril4Amaia Rodríguez5Jorge Baixauli6Gabriel Reina7Ana Sancho8Camilo Silva9Javier A. Cienfuegos10Gema Frühbeck11Metabolic Research Laboratory, Clínica Universidad de NavarraMetabolic Research Laboratory, Clínica Universidad de NavarraMetabolic Research Laboratory, Clínica Universidad de NavarraMetabolic Research Laboratory, Clínica Universidad de NavarraMetabolic Research Laboratory, Clínica Universidad de NavarraMetabolic Research Laboratory, Clínica Universidad de NavarraDepartment of Surgery, Clínica Universidad de NavarraDepartment of Microbiology, Clínica Universidad de NavarraBiomedical Engineering and Science Department, University of Navarra, TECNUN School of EngineeringCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos IIICIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos IIIMetabolic Research Laboratory, Clínica Universidad de NavarraAbstract Background PIEZO1 has emerged as a mechanoreceptor linked with adipogenesis, adipose tissue (AT) inflammation and insulin resistance. We aimed to determine the impact of obesity and obesity-associated type 2 diabetes (T2D) as well as mechanical compression forces on the expression of PIEZO1 in visceral AT (VAT) and its relation with inflammation. Methods Blood and VAT samples were obtained from 100 volunteers. Static compression studies in VAT explants were performed to study the PIEZO1 response. The effect of bariatric surgery on the expression of Piezo1 was assessed in a rat model of diet-induced obesity. Results Obesity and obesity-associated T2D increased (P < 0.01) gene expression levels of PIEZO1 in VAT mainly due to adipocytes. SWELL1 and key markers of inflammation (NLRP3, NLRP6, IL1B, IL18 and IL8) were also upregulated in VAT in obesity and T2D being significantly associated (P < 0.01) with PIEZO1 levels. We further showed that the static compression of VAT explants promoted an upregulation of PIEZO1 (P < 0.01) and SWELL1 (P < 0.01) expression levels together with a strong increase in the expression and release of key inflammatory mediators. The treatment of THP-1-derived macrophages with the secretome of adipocytes from patients with obesity upregulated (P < 0.001) PIEZO1 levels. Rats undergoing bariatric surgery exhibited decreased (P < 0.01) expression levels of Piezo1 in the epididymal AT. Conclusions Static compression triggered an upregulation of PIEZO1 in VAT explants together with a strong inflammation. In addition, the increased expression of PIEZO1 in VAT in obesity and obesity-associated T2D, primarily attributable to adipocytes, is closely associated with SWELL1 and inflammatory markers.https://doi.org/10.1186/s10020-024-01008-1PIEZO1VATMechanotransductionInflammationObesityType 2 diabetes
spellingShingle Victoria Catalán
Javier Gómez-Ambrosi
Beatriz Ramírez
Xabier Unamuno
Sara Becerril
Amaia Rodríguez
Jorge Baixauli
Gabriel Reina
Ana Sancho
Camilo Silva
Javier A. Cienfuegos
Gema Frühbeck
Increased expression levels of PIEZO1 in visceral adipose tissue in obesity and type 2 diabetes are triggered by mechanical forces and are associated with inflammation
Molecular Medicine
PIEZO1
VAT
Mechanotransduction
Inflammation
Obesity
Type 2 diabetes
title Increased expression levels of PIEZO1 in visceral adipose tissue in obesity and type 2 diabetes are triggered by mechanical forces and are associated with inflammation
title_full Increased expression levels of PIEZO1 in visceral adipose tissue in obesity and type 2 diabetes are triggered by mechanical forces and are associated with inflammation
title_fullStr Increased expression levels of PIEZO1 in visceral adipose tissue in obesity and type 2 diabetes are triggered by mechanical forces and are associated with inflammation
title_full_unstemmed Increased expression levels of PIEZO1 in visceral adipose tissue in obesity and type 2 diabetes are triggered by mechanical forces and are associated with inflammation
title_short Increased expression levels of PIEZO1 in visceral adipose tissue in obesity and type 2 diabetes are triggered by mechanical forces and are associated with inflammation
title_sort increased expression levels of piezo1 in visceral adipose tissue in obesity and type 2 diabetes are triggered by mechanical forces and are associated with inflammation
topic PIEZO1
VAT
Mechanotransduction
Inflammation
Obesity
Type 2 diabetes
url https://doi.org/10.1186/s10020-024-01008-1
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