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Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation

Aquaporin-11 (AQP11) is expressed in human adipocytes, but its functional role remains unknown. Since AQP11 is an endoplasmic reticulum (ER)-resident protein that transports water, glycerol, and hydrogen peroxide (H(2)O(2)), we hypothesized that this superaquaporin is involved in ER stress induced b...

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Autores principales: Frühbeck, Gema, Balaguer, Inmaculada, Méndez-Giménez, Leire, Valentí, Víctor, Becerril, Sara, Catalán, Victoria, Gómez-Ambrosi, Javier, Silva, Camilo, Salvador, Javier, Calamita, Giuseppe, Malagón, María M., Rodríguez, Amaia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349025/
https://www.ncbi.nlm.nih.gov/pubmed/32512939
http://dx.doi.org/10.3390/cells9061403
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author Frühbeck, Gema
Balaguer, Inmaculada
Méndez-Giménez, Leire
Valentí, Víctor
Becerril, Sara
Catalán, Victoria
Gómez-Ambrosi, Javier
Silva, Camilo
Salvador, Javier
Calamita, Giuseppe
Malagón, María M.
Rodríguez, Amaia
author_facet Frühbeck, Gema
Balaguer, Inmaculada
Méndez-Giménez, Leire
Valentí, Víctor
Becerril, Sara
Catalán, Victoria
Gómez-Ambrosi, Javier
Silva, Camilo
Salvador, Javier
Calamita, Giuseppe
Malagón, María M.
Rodríguez, Amaia
author_sort Frühbeck, Gema
collection PubMed
description Aquaporin-11 (AQP11) is expressed in human adipocytes, but its functional role remains unknown. Since AQP11 is an endoplasmic reticulum (ER)-resident protein that transports water, glycerol, and hydrogen peroxide (H(2)O(2)), we hypothesized that this superaquaporin is involved in ER stress induced by lipotoxicity and inflammation in human obesity. AQP11 expression was assessed in 67 paired visceral and subcutaneous adipose tissue samples obtained from patients with morbid obesity and normal-weight individuals. We found that obesity and obesity-associated type 2 diabetes increased (p < 0.05) AQP11 mRNA and protein in visceral adipose tissue, but not subcutaneous fat. Accordingly, AQP11 mRNA was upregulated (p < 0.05) during adipocyte differentiation and lipolysis, two biological processes altered in the obese state. Subcellular fractionation and confocal microscopy studies confirmed its presence in the ER plasma membrane of visceral adipocytes. Proinflammatory factors TNF-α, and particularly TGF-β1, downregulated (p < 0.05) AQP11 mRNA and protein expression and reinforced its subcellular distribution surrounding lipid droplets. Importantly, the AQP11 gene knockdown increased (p < 0.05) basal and TGF-β1-induced expression of the ER markers ATF4 and CHOP. Together, the downregulation of AQP11 aggravates TGF-β1-induced ER stress in visceral adipocytes. Owing to its “peroxiporin” properties, AQP11 overexpression in visceral fat might constitute a compensatory mechanism to alleviate ER stress in obesity.
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spelling pubmed-73490252020-07-22 Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation Frühbeck, Gema Balaguer, Inmaculada Méndez-Giménez, Leire Valentí, Víctor Becerril, Sara Catalán, Victoria Gómez-Ambrosi, Javier Silva, Camilo Salvador, Javier Calamita, Giuseppe Malagón, María M. Rodríguez, Amaia Cells Article Aquaporin-11 (AQP11) is expressed in human adipocytes, but its functional role remains unknown. Since AQP11 is an endoplasmic reticulum (ER)-resident protein that transports water, glycerol, and hydrogen peroxide (H(2)O(2)), we hypothesized that this superaquaporin is involved in ER stress induced by lipotoxicity and inflammation in human obesity. AQP11 expression was assessed in 67 paired visceral and subcutaneous adipose tissue samples obtained from patients with morbid obesity and normal-weight individuals. We found that obesity and obesity-associated type 2 diabetes increased (p < 0.05) AQP11 mRNA and protein in visceral adipose tissue, but not subcutaneous fat. Accordingly, AQP11 mRNA was upregulated (p < 0.05) during adipocyte differentiation and lipolysis, two biological processes altered in the obese state. Subcellular fractionation and confocal microscopy studies confirmed its presence in the ER plasma membrane of visceral adipocytes. Proinflammatory factors TNF-α, and particularly TGF-β1, downregulated (p < 0.05) AQP11 mRNA and protein expression and reinforced its subcellular distribution surrounding lipid droplets. Importantly, the AQP11 gene knockdown increased (p < 0.05) basal and TGF-β1-induced expression of the ER markers ATF4 and CHOP. Together, the downregulation of AQP11 aggravates TGF-β1-induced ER stress in visceral adipocytes. Owing to its “peroxiporin” properties, AQP11 overexpression in visceral fat might constitute a compensatory mechanism to alleviate ER stress in obesity. MDPI 2020-06-04 /pmc/articles/PMC7349025/ /pubmed/32512939 http://dx.doi.org/10.3390/cells9061403 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Frühbeck, Gema
Balaguer, Inmaculada
Méndez-Giménez, Leire
Valentí, Víctor
Becerril, Sara
Catalán, Victoria
Gómez-Ambrosi, Javier
Silva, Camilo
Salvador, Javier
Calamita, Giuseppe
Malagón, María M.
Rodríguez, Amaia
Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation
title Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation
title_full Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation
title_fullStr Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation
title_full_unstemmed Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation
title_short Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation
title_sort aquaporin-11 contributes to tgf-β1-induced endoplasmic reticulum stress in human visceral adipocytes: role in obesity-associated inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349025/
https://www.ncbi.nlm.nih.gov/pubmed/32512939
http://dx.doi.org/10.3390/cells9061403
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