ADAR2 deficiency ameliorates non-alcoholic fatty liver disease and muscle atrophy through modulating serum amyloid A1

作     者：Kung, Mei-Lang Yang, Tai-Hua Lin, Chia-Chi Ho, Jia-Yun Hung, Tzu-Chi Chang, Chih-Hsiang Huang, Kuan-Wen Chen, Chien-Chin Chen, Yun-Wen 

作者机构：Department of Medical Education and Research Kaohsiung Veterans General Hospital Kaohsiung Taiwan Department of Biomedical Engineering College of Engineering National Cheng Kung University Tainan Taiwan Department of Orthopedic Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan Department of Pharmacology College of Medicine National Cheng Kung University Tainan Taiwan Department of Pathology Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi Taiwan Department of Cosmetic Science Chia Nan University of Pharmacy and Science Tainan Taiwan Ph.D. Program in Translational Medicine Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung Taiwan Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan Taiwan 

出 版 物：《Journal of Cachexia, Sarcopenia and Muscle》 (J. Cachexia Sarcopenia Muscle)

年 卷 期：2024年第15卷第3期

页      面：949-962页

学科分类：0710[理学-生物学] 0403[教育学-体育学] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Ministry of Science and Technology, Taiwan, MOST, (112‐2320‐B‐006‐029‐MY3, 109‐2320‐B‐006‐041‐MY3, 106‐2320‐B‐006‐058‐MY3) Ministry of Science and Technology, Taiwan, MOST Kaohsiung Veterans General Hospital, KSVGH, (VGHNCKU111‐001) Kaohsiung Veterans General Hospital, KSVGH National Cheng Kung University Hospital, NCKU, (NCKUH‐11202036) National Cheng Kung University Hospital, NCKU 

主　　题：ADAR2 diabetes inflammation muscle atrophy NAFLD SAA1 

摘      要：Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with NAFLD. Adenosine-to-inosine editing, catalysed by adenosine deaminase acting on RNA (ADAR), is an important post-transcriptional modification of genome-encoded RNA transcripts. Three ADAR gene family members, including ADAR1, ADAR2 and ADAR3, have been identified. However, the functional role of ADAR2 in obesity-associated NAFLD and sarcopenia remains unclear. Methods: ADAR2+/+/GluR-BR/R mice (wild type [WT]) and ADAR2−/−/GluR-BR/R mice (ADAR2 knockout [KO]) were subjected to feeding with standard chow or high-fat diet (HFD) for 20 weeks at the age of 5 weeks. The metabolic parameters, hepatic lipid droplet, grip strength test, rotarod test, muscle weight, fibre cross-sectional area (CSA), fibre types and protein associated with protein degradation were examined. Systemic and local tissues serum amyloid A1 (SAA1) were measured. The effects of SAA1 on C2C12 myotube atrophy were investigated. Results: ADAR2 KO mice fed with HFD exhibited lower body weight (−7.7%, P 0.05), lower liver tissue weight (−20%, P 0.05), reduced liver lipid droplets in concert with a decrease in hepatic triglyceride content (−24%, P 0.001) and liver injury (P 0.01). ADAR2 KO mice displayed protection against HFD-induced glucose intolerance, insulin resistance and dyslipidaemia. Skeletal muscle mass (P 0.01), muscle strength (P 0.05), muscle endurance (P 0.001) and fibre size (CSA;P 0.0001) were improved in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. Muscle atrophy-associated transcripts, such as forkhead box protein O1, muscle atrophy F-box/atrogin-1 and muscle RING finger 1/tripartite motif-containing 63, were decreased in ADAR2 KO mice fed with HFD compare