| Texto completo | |
| Autor(es): |
da Costa, Rafael Menezes
;
Neves, Karla Bianca
;
Mestriner, Fabiola Leslie
;
Louzada-Junior, Paulo
;
Bruder-Nascimento, Thiago
;
Tostes, Rita C.
Número total de Autores: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | CARDIOVASCULAR DIABETOLOGY; v. 15, AUG 25 2016. |
| Citações Web of Science: | 15 |
| Resumo | |
Background: High fat diet (HFD) induces insulin resistance in various tissues, including the vasculature. HFD also increases plasma levels of TNF-alpha, a cytokine that contributes to insulin resistance and vascular dysfunction. Considering that the enzyme phosphatase and tension homologue (PTEN), whose expression is increased by TNF-alpha, reduces Akt signaling and, consequently, nitric oxide (NO) production, we hypothesized that PTEN contributes to TNF-alpha-mediated vascular resistance to insulin induced by HFD. Mechanisms underlying PTEN effects were determined. Methods: Mesenteric vascular beds were isolated from C57Bl/6J and TNF-alpha KO mice submitted to control or HFD diet for 18 weeks to assess molecular mechanisms by which TNF-alpha and PTEN contribute to vascular dysfunction. Results: Vasodilation in response to insulin was decreased in HFD-fed mice and in ex vivo control arteries incubated with TNF-alpha. TNF-alpha receptors deficiency and TNF-alpha blockade with infliximab abolished the effects of HFD and TNF-alpha on insulin-induced vasodilation. PTEN vascular expression (total and phosphorylated isoforms) was increased in HFD-fed mice. Treatment with a PTEN inhibitor improved insulin-induced vasodilation in HFD-fed mice. TNF-alpha receptor deletion restored PTEN expression/activity and Akt/eNOS/NO signaling in HFD-fed mice. Conclusion: TNF-alpha induces vascular insulin resistance by mechanisms that involve positive modulation of PTEN and inhibition of Akt/eNOS/NO signaling. Our findings highlight TNF-alpha and PTEN as potential targets to limit insulin resistance and vascular complications associated with obesity-related conditions. (AU) | |
| Processo FAPESP: | 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias |
| Beneficiário: | Fernando de Queiroz Cunha |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |