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 center dot signaling by activating the insulin pathway. These results suggest this hormone may be a determinant regulator of the beneficial effects of CR.

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Instituto Nacional de Ciencia e Tecnologia de Processos Redox em Biomedicina (Redoxoma)

Instituto Nacional de Ciencia e Tecnologia de Processos Redox em Biomedicina (Redoxoma)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

Coordenacao de Aperfeicoamento do Pessoal de Nivel Superior (CAPES)

Coordenacao de Aperfeicoamento do Pessoal de Nivel Superior (CAPES)

John Simon Guggenheim Memorial Foundation

John Simon Guggenheim Memorial Foundation