title: Mas deficiency in FVB/N mice produces marked changes in lipid and glycemic metabolism.
abstract: OBJECTIVE
  Metabolic syndrome is characterized by the variable coexistence of obesity, hyperinsulinemia, insulin resistance, dyslipidemia, and hypertension. It is well known that angiotensin (Ang) II is importantly involved in the metabolic syndrome. However, the role of the vasodilator Ang-(1-7)/Mas axis is not known. The aim of this study was to evaluate the effect of genetic deletion of the G protein-coupled receptor, Mas, in the lipidic and glycemic metabolism in FVB/N mice.
  
  
  METHODS
  Plasma lipid, insulin, and cytokine concentrations were measured in FVB/N Mas-deficient and wild-type mice. A glucose tolerance test was performed by intraperitoneally injecting d-glucose into overnight-fasted mice. An insulin sensitivity test was performed by intraperitoneal injection of insulin. Uptake of 2-deoxy-[(3)H]glucose by adipocytes was used to determine the rate of glucose transport; adipose tissue GLUT4 was quantified by Western blot. Gene expression of transforming growth factor (TGF)-beta, type 1 Ang II receptor, and angiotensinogen (AGT) were measured by real-time PCR.
  
  
  RESULTS
  Despite normal body weight, Mas-knockout (Mas-KO) mice presented dyslipidemia, increased levels of insulin and leptin, and an approximately 50% increase in abdominal fat mass. In addition, Mas gene-deleted mice presented glucose intolerance and reduced insulin sensitivity as well as a decrease in insulin-stimulated glucose uptake by adipocytes and decreased GLUT4 in adipose tissue. Mas(-/-) presented increased muscle triglycerides, while liver triglyceride levels were normal. Expression of TGF-beta and AGT genes was higher in Mas-KO animals in comparison with controls.
  
  
  CONCLUSIONS
  These results show that Mas deficiency in FVB/N mice leads to dramatic changes in glucose and lipid metabolisms, inducing a metabolic syndrome-like state.
authors.affiliation: Laborátorio de Hipertensão, Departamento de Fisiologia e Biofisica, Universidade Federal de Minas Gerais, Av Antonio Carlos 6627-ICB, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Sérgio Henrique S
authors.initials: SH
authors.lastname: Santos
authors.forename: Luciana Rodrigues
authors.initials: LR
authors.lastname: Fernandes
authors.forename: Erica Guilhen
authors.initials: EG
authors.lastname: Mario
authors.forename: Adaliene Versiani M
authors.initials: AV
authors.lastname: Ferreira
authors.forename: Laura Cristina J
authors.initials: LC
authors.lastname: Pôrto
authors.forename: Jaqueline Isaura
authors.initials: JI
authors.lastname: Alvarez-Leite
authors.forename: Leida Maria
authors.initials: LM
authors.lastname: Botion
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.forename: Robson Augusto S
authors.initials: RA
authors.lastname: Santos
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000502:physiology; D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D016207:Cytokines / Q000097:blood; D002149:Energy Intake; D004822:Epididymis / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood*; D008055:Lipids / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D008055:Lipids; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D014280:Triglycerides; D005947:Glucose