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CD36/sirtuin 1 axis impairment contributes to hepatic steatosis in ACE2-deficient mice

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Item Type:Article
Title:CD36/sirtuin 1 axis impairment contributes to hepatic steatosis in ACE2-deficient mice
Creators Name:Nunes-Souza, V., Alenina, N., Qadri, F., Penninger, J.M., Santos, R.A.S., Bader, M. and Rabelo, L.A.
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.
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
Source:Oxidative Medicine and Cellular Longevity
ISSN:1942-0900
Publisher:Hindawi
Volume:2016
Page Range:6487509
Date:2016
Official Publication:https://doi.org/10.1155/2016/6487509
PubMed:View item in PubMed

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