Serum from calorie-restricted rats activates vascular cell eNOS through enhanced insulin signaling mediated by adiponectin.
eNOS activation resulting in mitochondrial biogenesis is believed to play a central role in life span extension promoted by calorie restriction (CR). We investigated the mechanism of this activation by treating vascular cells with serum from CR rats and found increased Akt and eNOS phosphorylation, in addition to enhanced nitrite release. Inhibiting Akt phosphorylation or immunoprecipitating adiponectin (found in high quantities in CR serum) completely prevented the increment in nitrite release and eNOS activation. Overall, we demonstrate that adiponectin in the serum from CR animals increases NO• signaling by activating the insulin pathway. These results suggest this hormone may be a determinant regulator of the beneficial effects of CR.
Instituto de Química, Departamento de Bioquímica, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
Fernanda M
FM
Cerqueira
Laura I
LI
Brandizzi
Fernanda M
FM
Cunha
Francisco R M
FR
Laurindo
Alicia J
AJ
Kowaltowski
D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D007328:Insulin / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction
D052242:Adiponectin; D007328:Insulin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051058:Oncogene Protein v-akt