Cargando…
Angiotensin Converting Enzyme‐2 Therapy Improves Liver Fibrosis and Glycemic Control in Diabetic Mice With Fatty Liver
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is frequently associated with type 2 diabetes. However, there is no specific medical therapy to treat this condition. Angiotensin‐converting enzyme 2 (ACE2) of the protective renin angiotensin system gener...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035567/ https://www.ncbi.nlm.nih.gov/pubmed/34951153 http://dx.doi.org/10.1002/hep4.1884 |
_version_ | 1784693321574121472 |
---|---|
author | Rajapaksha, Indu G. Gunarathne, Lakmie S. Asadi, Khashayar Laybutt, Ross Andrikopoulous, Sof Alexander, Ian E. Watt, Mathew J. Angus, Peter W. Herath, Chandana B. |
author_facet | Rajapaksha, Indu G. Gunarathne, Lakmie S. Asadi, Khashayar Laybutt, Ross Andrikopoulous, Sof Alexander, Ian E. Watt, Mathew J. Angus, Peter W. Herath, Chandana B. |
author_sort | Rajapaksha, Indu G. |
collection | PubMed |
description | Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is frequently associated with type 2 diabetes. However, there is no specific medical therapy to treat this condition. Angiotensin‐converting enzyme 2 (ACE2) of the protective renin angiotensin system generates the antifibrotic peptide angiotensin‐(1‐7) from profibrotic angiotensin II peptide. In this study, we investigated the therapeutic potential of ACE2 in diabetic NAFLD mice fed a high‐fat (20%), high‐cholesterol (2%) diet for 40 weeks. Mice were given a single intraperitoneal injection of ACE2 using an adeno‐associated viral vector at 30 weeks of high‐fat, high‐cholesterol diet (15 weeks after induction of diabetes) and sacrificed 10 weeks later. ACE2 significantly reduced liver injury and fibrosis in diabetic NAFLD mice compared with the control vector injected mice. This was accompanied by reductions in proinflammatory cytokine expressions, hepatic stellate cell activation, and collagen 1 expression. Moreover, ACE2 therapy significantly increased islet numbers, leading to an increased insulin protein content in β‐cells and plasma insulin levels with subsequent reduction in plasma glucose levels compared with controls. Conclusion: We conclude that ACE2 gene therapy reduces liver fibrosis and hyperglycemia in diabetic NAFLD mice and has potential as a therapy for patients with NAFLD with diabetes. |
format | Online Article Text |
id | pubmed-9035567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90355672022-04-27 Angiotensin Converting Enzyme‐2 Therapy Improves Liver Fibrosis and Glycemic Control in Diabetic Mice With Fatty Liver Rajapaksha, Indu G. Gunarathne, Lakmie S. Asadi, Khashayar Laybutt, Ross Andrikopoulous, Sof Alexander, Ian E. Watt, Mathew J. Angus, Peter W. Herath, Chandana B. Hepatol Commun Original Articles Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is frequently associated with type 2 diabetes. However, there is no specific medical therapy to treat this condition. Angiotensin‐converting enzyme 2 (ACE2) of the protective renin angiotensin system generates the antifibrotic peptide angiotensin‐(1‐7) from profibrotic angiotensin II peptide. In this study, we investigated the therapeutic potential of ACE2 in diabetic NAFLD mice fed a high‐fat (20%), high‐cholesterol (2%) diet for 40 weeks. Mice were given a single intraperitoneal injection of ACE2 using an adeno‐associated viral vector at 30 weeks of high‐fat, high‐cholesterol diet (15 weeks after induction of diabetes) and sacrificed 10 weeks later. ACE2 significantly reduced liver injury and fibrosis in diabetic NAFLD mice compared with the control vector injected mice. This was accompanied by reductions in proinflammatory cytokine expressions, hepatic stellate cell activation, and collagen 1 expression. Moreover, ACE2 therapy significantly increased islet numbers, leading to an increased insulin protein content in β‐cells and plasma insulin levels with subsequent reduction in plasma glucose levels compared with controls. Conclusion: We conclude that ACE2 gene therapy reduces liver fibrosis and hyperglycemia in diabetic NAFLD mice and has potential as a therapy for patients with NAFLD with diabetes. John Wiley and Sons Inc. 2021-12-23 /pmc/articles/PMC9035567/ /pubmed/34951153 http://dx.doi.org/10.1002/hep4.1884 Text en © 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Rajapaksha, Indu G. Gunarathne, Lakmie S. Asadi, Khashayar Laybutt, Ross Andrikopoulous, Sof Alexander, Ian E. Watt, Mathew J. Angus, Peter W. Herath, Chandana B. Angiotensin Converting Enzyme‐2 Therapy Improves Liver Fibrosis and Glycemic Control in Diabetic Mice With Fatty Liver |
title | Angiotensin Converting Enzyme‐2 Therapy Improves Liver Fibrosis and Glycemic Control in Diabetic Mice With Fatty Liver |
title_full | Angiotensin Converting Enzyme‐2 Therapy Improves Liver Fibrosis and Glycemic Control in Diabetic Mice With Fatty Liver |
title_fullStr | Angiotensin Converting Enzyme‐2 Therapy Improves Liver Fibrosis and Glycemic Control in Diabetic Mice With Fatty Liver |
title_full_unstemmed | Angiotensin Converting Enzyme‐2 Therapy Improves Liver Fibrosis and Glycemic Control in Diabetic Mice With Fatty Liver |
title_short | Angiotensin Converting Enzyme‐2 Therapy Improves Liver Fibrosis and Glycemic Control in Diabetic Mice With Fatty Liver |
title_sort | angiotensin converting enzyme‐2 therapy improves liver fibrosis and glycemic control in diabetic mice with fatty liver |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035567/ https://www.ncbi.nlm.nih.gov/pubmed/34951153 http://dx.doi.org/10.1002/hep4.1884 |
work_keys_str_mv | AT rajapakshaindug angiotensinconvertingenzyme2therapyimprovesliverfibrosisandglycemiccontrolindiabeticmicewithfattyliver AT gunarathnelakmies angiotensinconvertingenzyme2therapyimprovesliverfibrosisandglycemiccontrolindiabeticmicewithfattyliver AT asadikhashayar angiotensinconvertingenzyme2therapyimprovesliverfibrosisandglycemiccontrolindiabeticmicewithfattyliver AT laybuttross angiotensinconvertingenzyme2therapyimprovesliverfibrosisandglycemiccontrolindiabeticmicewithfattyliver AT andrikopouloussof angiotensinconvertingenzyme2therapyimprovesliverfibrosisandglycemiccontrolindiabeticmicewithfattyliver AT alexanderiane angiotensinconvertingenzyme2therapyimprovesliverfibrosisandglycemiccontrolindiabeticmicewithfattyliver AT wattmathewj angiotensinconvertingenzyme2therapyimprovesliverfibrosisandglycemiccontrolindiabeticmicewithfattyliver AT anguspeterw angiotensinconvertingenzyme2therapyimprovesliverfibrosisandglycemiccontrolindiabeticmicewithfattyliver AT herathchandanab angiotensinconvertingenzyme2therapyimprovesliverfibrosisandglycemiccontrolindiabeticmicewithfattyliver |