CD36/sirtuin 1 axis impairment contributes to hepatic steatosis in ACE2-deficient mice
Item Type: | Article |
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Title: | CD36/sirtuin 1 axis impairment contributes to hepatic steatosis in ACE2-deficient mice |
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Creators Name: | Nunes-Souza, V. and Alenina, N. and Qadri, F. and Penninger, J.M. and Santos, R.A.S. and Bader, M. and Rabelo, L.A. |
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Abstract: | Background and Aims. Angiotensin converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system. Since angiotensin peptides have been shown to be involved in hepatic steatosis, we aimed to evaluate the hepatic lipid profile in ACE2- deficient (ACE2−/y) mice. Methods. Male C57BL/6 andACE2−/y mice were analyzed at the age of 3 and 6 months for alterations in the lipid profiles of plasma, faeces, and liver and for hepatic steatosis. Results. ACE2−/y mice showed lower body weight and white adipose tissue at all ages investigated. Moreover, these mice had lower levels of cholesterol, triglycerides, and nonesterified fatty acids in plasma. Strikingly, ACE2−/y mice showed high deposition of lipids in the liver. Expression of CD36, a protein involved in the uptake of triglycerides in liver, was increased in ACE2−/y mice. Concurrently, these mice exhibited an increase in hepatic oxidative stress, evidenced by increased lipid peroxidation and expression of uncoupling protein 2, and downregulation of sirtuin 1. ACE2−/y mice also showed impairments in glucose metabolism and insulin signaling in the liver. Conclusions. Deletion of ACE2 causes CD36/sirtuin 1 axis impairment and thereby interferes with lipid homeostasis, leading to lipodystrophy and steatosis. |
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Keywords: | Body Weight, CD36 Antigens, Catalase, Cholesterol, Down-Regulation, Fatty Liver, Gluconeogenesis, Insulin, Lipid Peroxidation, Liver, Messenger RNA, Nonesterified Fatty Acids, Peptidyl-Dipeptidase A, Signal Transduction, Sirtuin 1, Superoxide Dismutase, Triglycerides, Animals, Mice |
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Source: | Oxidative Medicine and Cellular Longevity |
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ISSN: | 1942-0900 |
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Publisher: | Hindawi |
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Volume: | 2016 |
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Page Range: | 6487509 |
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Date: | 2016 |
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Official Publication: | https://doi.org/10.1155/2016/6487509 |
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PubMed: | View item in PubMed |
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