dc.creatorCosta, Rafael Menezes da
dc.creatorNeves, Karla Bianca
dc.creatorMestriner, Fabíola Leslie
dc.creatorLouzada-Junior, Paulo
dc.creatorBruder-Nascimento, Thiago
dc.creatorTostes, Rita C.
dc.date.accessioned2016-08-25T18:02:08Z
dc.date.accessioned2018-07-04T17:11:38Z
dc.date.available2016-08-25T18:02:08Z
dc.date.available2018-07-04T17:11:38Z
dc.date.created2016-08-25T18:02:08Z
dc.date.issued2016
dc.identifierCardiovascular Diabetology. 2016 Aug 25;15(1):119
dc.identifierhttp://dx.doi.org/10.1186/s12933-016-0443-0
dc.identifierhttp://www.producao.usp.br/handle/BDPI/50600
dc.identifier10.1186/s12933-016-0443-0
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1645931
dc.description.abstractAbstract Background High fat diet (HFD) induces insulin resistance in various tissues, including the vasculature. HFD also increases plasma levels of TNF-α, 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-α, reduces Akt signaling and, consequently, nitric oxide (NO) production, we hypothesized that PTEN contributes to TNF-α-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-α KO mice submitted to control or HFD diet for 18 weeks to assess molecular mechanisms by which TNF-α 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-α. TNF-α receptors deficiency and TNF-α blockade with infliximab abolished the effects of HFD and TNF-α 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-α receptor deletion restored PTEN expression/activity and Akt/eNOS/NO signaling in HFD-fed mice. Conclusion TNF-α induces vascular insulin resistance by mechanisms that involve positive modulation of PTEN and inhibition of Akt/eNOS/NO signaling. Our findings highlight TNF-α and PTEN as potential targets to limit insulin resistance and vascular complications associated with obesity-related conditions.
dc.languageen
dc.publisherBioMed Central
dc.relationCardiovascular Diabetology
dc.rightsThe Author(s)
dc.rightsopenAccess
dc.subjectHigh fat diet
dc.subjectInsulin
dc.subjectTNF-α
dc.subjectPTEN
dc.subjectVascular function
dc.titleTNF-α induces vascular insulin resistance via positive modulation of PTEN and decreased Akt/eNOS/NO signaling in high fat diet-fed mice
dc.typeArtículos de revistas


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