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<sub>2</sub>O<sub>2</sub>), we hypothesized that this superaq...
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MDPI AG
2020-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/6/1403 |
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| author | Gema Frühbeck Inmaculada Balaguer Leire Méndez-Giménez Víctor Valentí Sara Becerril Victoria Catalán Javier Gómez-Ambrosi Camilo Silva Javier Salvador Giuseppe Calamita María M. Malagón Amaia Rodríguez |
| author_facet | Gema Frühbeck Inmaculada Balaguer Leire Méndez-Giménez Víctor Valentí Sara Becerril Victoria Catalán Javier Gómez-Ambrosi Camilo Silva Javier Salvador Giuseppe Calamita María M. Malagón Amaia Rodríguez |
| author_sort | Gema Frühbeck |
| collection | DOAJ |
| 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<sub>2</sub>O<sub>2</sub>), 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 (<i>p</i> < 0.05) AQP11 mRNA and protein in visceral adipose tissue, but not subcutaneous fat. Accordingly, <i>AQP11</i> mRNA was upregulated (<i>p</i> < 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 (<i>p</i> < 0.05) AQP11 mRNA and protein expression and reinforced its subcellular distribution surrounding lipid droplets. Importantly, the <i>AQP11</i> gene knockdown increased (<i>p</i> < 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. |
| first_indexed | 2024-03-10T19:21:44Z |
| format | Article |
| id | doaj.art-560dd981320e42fe8db77aa939008539 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:21:44Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-560dd981320e42fe8db77aa9390085392023-11-20T02:54:05ZengMDPI AGCells2073-44092020-06-0196140310.3390/cells9061403Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated InflammationGema Frühbeck0Inmaculada Balaguer1Leire Méndez-Giménez2Víctor Valentí3Sara Becerril4Victoria Catalán5Javier Gómez-Ambrosi6Camilo Silva7Javier Salvador8Giuseppe Calamita9María M. Malagón10Amaia Rodríguez11Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, SpainDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “Aldo Moro”, 70125 Bari, ItalyCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainAquaporin-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<sub>2</sub>O<sub>2</sub>), 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 (<i>p</i> < 0.05) AQP11 mRNA and protein in visceral adipose tissue, but not subcutaneous fat. Accordingly, <i>AQP11</i> mRNA was upregulated (<i>p</i> < 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 (<i>p</i> < 0.05) AQP11 mRNA and protein expression and reinforced its subcellular distribution surrounding lipid droplets. Importantly, the <i>AQP11</i> gene knockdown increased (<i>p</i> < 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.https://www.mdpi.com/2073-4409/9/6/1403aquaporinsobesityendoplasmic reticulum stress |
| spellingShingle | Gema Frühbeck Inmaculada Balaguer Leire Méndez-Giménez Víctor Valentí Sara Becerril Victoria Catalán Javier Gómez-Ambrosi Camilo Silva Javier Salvador Giuseppe Calamita María M. Malagón Amaia Rodríguez Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation Cells aquaporins obesity endoplasmic reticulum stress |
| 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 | aquaporins obesity endoplasmic reticulum stress |
| url | https://www.mdpi.com/2073-4409/9/6/1403 |
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