Improved lipid and glucose metabolism in transgenic rats with increased circulating angiotensin-(1-7).
OBJECTIVE
Obesity and diabetes remain among the world's most pervasive health problems. Although the importance of angiotensin II for metabolic regulation is well documented, the role of the angiotensin-(1-7)/Mas axis in this process is poorly understood. The aim of this study was to evaluate the effect of increased angiotensin-(1-7) plasma levels in lipid and glucose metabolism using transgenic rats that express an angiotensin-(1-7)-releasing fusion protein, TGR(A1-7)3292 (TGR).


RESULTS
The increased angiotensin-(1-7) levels in TGR induced enhanced glucose tolerance, insulin sensitivity, and insulin-stimulated glucose uptake. In addition, TGR presented decreased triglycerides and cholesterol levels, as well as a significant decrease in abdominal fat mass, despite normal food intake. These alterations were accompanied by a marked decrease of angiotensinogen expression and increased Akt in adipose tissue. Furthermore, augmented plasma levels and expression in adipose tissue was observed for adiponectin. Accordingly, angiotensin-(1-7) stimulation increased adiponectin production by primary adipocyte culture, which was blocked by the Mas antagonist A779. Circulating insulin and muscle glycogen content were not altered in TGR.


CONCLUSIONS
These results show that increased circulating angiotensin-(1-7) levels lead to prominent changes in glucose and lipid metabolism.
Santos
Sérgio Henrique S
SH
Laboratory of Hypertension, INCT-NanoBiofar, Minas Gerais, Brazil.
Braga
Janaina Felix
JF
Mario
Erica Guilhen
EG
Pôrto
Laura Cristina J
LC
Rodrigues-Machado
Maria da Glória
Mda G
Murari
Antonela
A
Botion
Leida Maria
LM
Alenina
Natalia
N
Bader
Michael
M
Santos
Robson Augusto S
RA
D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050154:Adiposity; D000803:Angiotensin I; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001835:Body Weight; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008297:Male; D010446:Peptide Fragments / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
C092006:7-Ala-angiotensin (1-7); D052242:Adiponectin; C499920:Adipoq protein, rat; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D014280:Triglycerides; D000804:Angiotensin II; D000803:Angiotensin I; D002784:Cholesterol; D051057:Proto-Oncogene Proteins c-akt; C118790:angiotensin I (1-7)