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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7349025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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