Inhibition of Hypothalamic Inflammation Reverses Diet-Induced Insulin Resistance in the Liver

dc.creatorMilanski, M
dc.creatorArruda, AP
dc.creatorCoope, A
dc.creatorIgnacio-Souza, LM
dc.creatorNunez, CE
dc.creatorRoman, EA
dc.creatorRomanatto, T
dc.creatorPascoal, LB
dc.creatorCaricilli, AM
dc.creatorTorsoni, MA
dc.creatorPrada, PO
dc.creatorSaad, MJ
dc.creatorVelloso, LA
dc.date2012
dc.dateJUN
dc.date2014-08-01T18:32:55Z
dc.date2015-11-26T17:59:54Z
dc.date2014-08-01T18:32:55Z
dc.date2015-11-26T17:59:54Z
dc.date.accessioned2018-03-29T00:42:27Z
dc.date.available2018-03-29T00:42:27Z
dc.identifierDiabetes. Amer Diabetes Assoc, v. 61, n. 6, n. 1455, n. 1462, 2012.
dc.identifier0012-1797
dc.identifierWOS:000304490100022
dc.identifier10.2337/db11-0390
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/80585
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/80585
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1291849
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionDefective liver gluconeogenesis is the main mechanism leading to fasting hyperglycemia in type 2 diabetes, and, in concert with steatosis, it is the hallmark of hepatic insulin resistance. Experimental obesity results, at least in part, from hypothalamic inflammation, which leads to leptin resistance and defective regulation of energy homeostasis. Pharmacological or genetic disruption of hypothalamic inflammation restores leptin sensitivity and reduces adiposity. Here, we evaluate the effect of a hypothalamic anti-inflammatory approach to regulating hepatic responsiveness to insulin. Obese rodents were treated by intracerebroventricular injections, with immunoneutralizing antibodies against Toll-like receptor (TLR) 4 or tumor necrosis factor (TNF)alpha, and insulin signal transduction, hepatic steatosis, and gluconeogenesis were evaluated. The inhibition of either TLR4 or TNF alpha reduced hypothalamic inflammation, which was accompanied by the reduction of hypothalamic resistance to leptin and improved insulin signal transduction in the liver. This was accompanied by reduced liver steatosis and reduced hepatic expression of markers of steatosis. Furthermore, the inhibition of hypothalamic inflammation restored defective liver glucose production. All these beneficial effects were abrogated by vagotomy. Thus, the inhibition of hypothalamic inflammation in obesity results in improved hepatic insulin signal transduction, leading to reduced steatosis and reduced gluconeogenesis. All these effects are mediated by parasympathetic signals delivered by the vagus nerve. Diabetes 61:1455-1462, 2012
dc.description61
dc.description6
dc.description1455
dc.description1462
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.languageen
dc.publisherAmer Diabetes Assoc
dc.publisherAlexandria
dc.publisherEUA
dc.relationDiabetes
dc.relationDiabetes
dc.rightsfechado
dc.sourceWeb of Science
dc.subjectHepatic Glucose-production
dc.subjectInduced Obesity
dc.subjectMice
dc.subjectLeptin
dc.subjectPathogenesis
dc.subjectSensitivity
dc.subjectMetabolism
dc.subjectMinireview
dc.subjectDisease
dc.subjectStress
dc.titleInhibition of Hypothalamic Inflammation Reverses Diet-Induced Insulin Resistance in the Liver
dc.typeArtículos de revistas


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