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Title: Angiotensin Converting Enzyme-2 Therapy Improves Liver Fibrosis and Glycemic Control in Diabetic Mice With Fatty Liver.
Austin Authors: Rajapaksha, Indu G;Gunarathne, Lakmie S;Asadi, Khashayar ;Laybutt, Ross;Andrikopoulous, Sof;Alexander, Ian E;Watt, Mathew J;Angus, Peter W ;Herath, Chandana B
Affiliation: Anatomical Pathology
Gastroenterology and Hepatology
Medicine (University of Melbourne)
School of Medicine, University of Sydney, Children's Medical Research Institute, Sydney, NSW, Australia
South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
Department Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, Australia
Garvan Institute of Medical Research, Sydney, NSW, Australia
St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
Issue Date: May-2022
Date: 2021-12-23
Publication information: Hepatology Communications 2022; 6(5): 1056-1072
Abstract: 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.
DOI: 10.1002/hep4.1884
ORCID: 0000-0002-3326-3654
Journal: Hepatology Communications
PubMed URL: 34951153
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

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