Mas deficiency in FVB/N mice produces marked changes in lipid and glycemic metabolism.
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.
Santos
Sérgio Henrique S
SH
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.
Fernandes
Luciana Rodrigues
LR
Mario
Erica Guilhen
EG
Ferreira
Adaliene Versiani M
AV
Pôrto
Laura Cristina J
LC
Alvarez-Leite
Jaqueline Isaura
JI
Botion
Leida Maria
LM
Bader
Michael
M
Alenina
Natalia
N
Santos
Robson Augusto S
RA
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
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