title: CD36/Sirtuin 1 Axis Impairment Contributes to Hepatic Steatosis in ACE2-Deficient Mice.
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 and ACE2-/ymice 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-/ymice 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-/ymice 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-/ymice. 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-/ymice 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.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany; Laboratório de Reatividade Cardiovascular (LRC), Núcleo de Síndrome Metabólica, Universidade Federal de Alagoas, Maceió, Brazil; National Institute of Science and Technology in Nano-Biopharmaceutics (N-BIOFAR), Belo Horizonte, Brazil; Departamento de Fisiologia e Farmacologia, Centro de Biociências (CB), Universidade Federal de Pernambuco, Recife, Brazil.
authors.forename: Valéria
authors.identifier: 0000-0002-5751-7751
authors.initials: V
authors.lastname: Nunes-Souza
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany; National Institute of Science and Technology in Nano-Biopharmaceutics (N-BIOFAR), Belo Horizonte, Brazil; Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Natalia
authors.identifier: 0000-0002-6071-5433
authors.initials: N
authors.lastname: Alenina
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Fatimunnisa
authors.initials: F
authors.lastname: Qadri
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.affiliation: National Institute of Science and Technology in Nano-Biopharmaceutics (N-BIOFAR), Belo Horizonte, Brazil; Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Robson Augusto S
authors.initials: RA
authors.lastname: Santos
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany; National Institute of Science and Technology in Nano-Biopharmaceutics (N-BIOFAR), Belo Horizonte, Brazil; Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Charité-University Medicine Berlin, Berlin, Germany; Institute for Biology, University of Lübeck, Lübeck, Germany; German Center for Cardiovascular Research (DZHK), Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany; Laboratório de Reatividade Cardiovascular (LRC), Núcleo de Síndrome Metabólica, Universidade Federal de Alagoas, Maceió, Brazil; National Institute of Science and Technology in Nano-Biopharmaceutics (N-BIOFAR), Belo Horizonte, Brazil.
authors.forename: Luiza A
authors.identifier: 0000-0001-9280-6527
authors.initials: LA
authors.lastname: Rabelo
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001835:Body Weight; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D015536:Down-Regulation; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism; D005943:Gluconeogenesis; D007328:Insulin / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D018955:CD36 Antigens; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol; D002374:Catalase; D013482:Superoxide Dismutase; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D056564:Sirtuin 1