iNOS gene ablation prevents liver fibrosis in leptin-deficient ob/ob mice
The role of extracellular matrix (ECM) remodeling in fibrosis progression in nonalcoholic fatty liver disease (NAFLD) is complex and dynamic, involving the synthesis and degradation of different ECM components, including tenascin C (TNC). The aim was to analyze the influence of inducible nitric oxid...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/63567 |
| Acceso en línea: | https://hdl.handle.net/10171/63567 |
| Access Level: | acceso abierto |
| Palabra clave: | Leptin iNOS Tenascin C Liver fibrosis Inflammation |
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iNOS gene ablation prevents liver fibrosis in leptin-deficient ob/ob miceBecerril-Mañas, S. (Sara)|||/items/5edb25ec-0edd-44eb-8ef1-c81d0ebd7300Rodriguez, A. (Amaia)|||/items/50976a5f-9842-47f1-8a9c-508e59996427Catalán-Goñi, V. (Victoria)|||/items/9a5a055c-323a-4b41-800f-65abf7f22c79Ramirez-Sola, B. (Beatriz)|||/items/95970833-a061-4e49-b5d8-e6ecc6ec59c4Unamuno, X. (Xabier)|||/items/15dc60c5-74df-4a3f-a0c0-7410321a8d3bGomez-Ambrosi, J. (Javier)|||/items/21d09997-940a-45f7-9b4b-0a9f64b2ed8eFrühbeck, G. (Gema)|||/items/7f0b1f72-bc91-4ab0-a3fd-21e9a3fb663bLeptiniNOSTenascin CLiver fibrosisInflammationThe role of extracellular matrix (ECM) remodeling in fibrosis progression in nonalcoholic fatty liver disease (NAFLD) is complex and dynamic, involving the synthesis and degradation of different ECM components, including tenascin C (TNC). The aim was to analyze the influence of inducible nitric oxide synthase (iNOS) deletion on inflammation and ECM remodeling in the liver of ob/ob mice, since a functional relationship between leptin and iNOS has been described. The expression of molecules involved in inflammation and ECM remodeling was analyzed in the liver of double knockout (DBKO) mice simultaneously lacking the ob and the iNOS genes. Moreover, the effect of leptin was studied in the livers of ob/ob mice and compared to wild-type rodents. Liver inflammation and fibrosis were increased in leptin-deficient mice. As expected, leptin treatment reverted the obesity phenotype. iNOS deletion in ob/ob mice improved insulin sensitivity, inflammation, and fibrogenesis, as evidenced by lower macrophage infiltration and collagen deposition as well as downregulation of the proinflammatory and profibrogenic genes including Tnc. Circulating TNC levels were also decreased. Furthermore, leptin upregulated TNC expression and release via NO-dependent mechanisms in AML12 hepatic cells. iNOS deficiency in ob/ob mice improved liver inflammation and ECM remodeling-related genes, decreasing fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in hepatocytes, suggesting an important role of this alarmin in the development of NAFLD.MDPI AGDadun. Depósito Académico Digital Universidad de Navarra20222022-05-2720192019-01-0120192019-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/63567reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/635672026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
iNOS gene ablation prevents liver fibrosis in leptin-deficient ob/ob mice |
| title |
iNOS gene ablation prevents liver fibrosis in leptin-deficient ob/ob mice |
| spellingShingle |
iNOS gene ablation prevents liver fibrosis in leptin-deficient ob/ob mice Becerril-Mañas, S. (Sara)|||/items/5edb25ec-0edd-44eb-8ef1-c81d0ebd7300 Leptin iNOS Tenascin C Liver fibrosis Inflammation |
| title_short |
iNOS gene ablation prevents liver fibrosis in leptin-deficient ob/ob mice |
| title_full |
iNOS gene ablation prevents liver fibrosis in leptin-deficient ob/ob mice |
| title_fullStr |
iNOS gene ablation prevents liver fibrosis in leptin-deficient ob/ob mice |
| title_full_unstemmed |
iNOS gene ablation prevents liver fibrosis in leptin-deficient ob/ob mice |
| title_sort |
iNOS gene ablation prevents liver fibrosis in leptin-deficient ob/ob mice |
| dc.creator.none.fl_str_mv |
Becerril-Mañas, S. (Sara)|||/items/5edb25ec-0edd-44eb-8ef1-c81d0ebd7300 Rodriguez, A. (Amaia)|||/items/50976a5f-9842-47f1-8a9c-508e59996427 Catalán-Goñi, V. (Victoria)|||/items/9a5a055c-323a-4b41-800f-65abf7f22c79 Ramirez-Sola, B. (Beatriz)|||/items/95970833-a061-4e49-b5d8-e6ecc6ec59c4 Unamuno, X. (Xabier)|||/items/15dc60c5-74df-4a3f-a0c0-7410321a8d3b Gomez-Ambrosi, J. (Javier)|||/items/21d09997-940a-45f7-9b4b-0a9f64b2ed8e Frühbeck, G. (Gema)|||/items/7f0b1f72-bc91-4ab0-a3fd-21e9a3fb663b |
| author |
Becerril-Mañas, S. (Sara)|||/items/5edb25ec-0edd-44eb-8ef1-c81d0ebd7300 |
| author_facet |
Becerril-Mañas, S. (Sara)|||/items/5edb25ec-0edd-44eb-8ef1-c81d0ebd7300 Rodriguez, A. (Amaia)|||/items/50976a5f-9842-47f1-8a9c-508e59996427 Catalán-Goñi, V. (Victoria)|||/items/9a5a055c-323a-4b41-800f-65abf7f22c79 Ramirez-Sola, B. (Beatriz)|||/items/95970833-a061-4e49-b5d8-e6ecc6ec59c4 Unamuno, X. (Xabier)|||/items/15dc60c5-74df-4a3f-a0c0-7410321a8d3b Gomez-Ambrosi, J. (Javier)|||/items/21d09997-940a-45f7-9b4b-0a9f64b2ed8e Frühbeck, G. (Gema)|||/items/7f0b1f72-bc91-4ab0-a3fd-21e9a3fb663b |
| author_role |
author |
| author2 |
Rodriguez, A. (Amaia)|||/items/50976a5f-9842-47f1-8a9c-508e59996427 Catalán-Goñi, V. (Victoria)|||/items/9a5a055c-323a-4b41-800f-65abf7f22c79 Ramirez-Sola, B. (Beatriz)|||/items/95970833-a061-4e49-b5d8-e6ecc6ec59c4 Unamuno, X. (Xabier)|||/items/15dc60c5-74df-4a3f-a0c0-7410321a8d3b Gomez-Ambrosi, J. (Javier)|||/items/21d09997-940a-45f7-9b4b-0a9f64b2ed8e Frühbeck, G. (Gema)|||/items/7f0b1f72-bc91-4ab0-a3fd-21e9a3fb663b |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Leptin iNOS Tenascin C Liver fibrosis Inflammation |
| topic |
Leptin iNOS Tenascin C Liver fibrosis Inflammation |
| description |
The role of extracellular matrix (ECM) remodeling in fibrosis progression in nonalcoholic fatty liver disease (NAFLD) is complex and dynamic, involving the synthesis and degradation of different ECM components, including tenascin C (TNC). The aim was to analyze the influence of inducible nitric oxide synthase (iNOS) deletion on inflammation and ECM remodeling in the liver of ob/ob mice, since a functional relationship between leptin and iNOS has been described. The expression of molecules involved in inflammation and ECM remodeling was analyzed in the liver of double knockout (DBKO) mice simultaneously lacking the ob and the iNOS genes. Moreover, the effect of leptin was studied in the livers of ob/ob mice and compared to wild-type rodents. Liver inflammation and fibrosis were increased in leptin-deficient mice. As expected, leptin treatment reverted the obesity phenotype. iNOS deletion in ob/ob mice improved insulin sensitivity, inflammation, and fibrogenesis, as evidenced by lower macrophage infiltration and collagen deposition as well as downregulation of the proinflammatory and profibrogenic genes including Tnc. Circulating TNC levels were also decreased. Furthermore, leptin upregulated TNC expression and release via NO-dependent mechanisms in AML12 hepatic cells. iNOS deficiency in ob/ob mice improved liver inflammation and ECM remodeling-related genes, decreasing fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in hepatocytes, suggesting an important role of this alarmin in the development of NAFLD. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019-01-01 2019 2019-01-01 2022 2022-05-27 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/63567 |
| url |
https://hdl.handle.net/10171/63567 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
MDPI AG |
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MDPI AG |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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