Cdc2-like Kinase 2 In The Hypothalamus Is Necessary To Maintain Energy Homeostasis

dc.creatorQuaresma
dc.creatorP. G. F.; Weissmann
dc.creatorL.; Zanotto
dc.creatorT. M.; Santos
dc.creatorA. C.; de Matos
dc.creatorA. H. B.; Furigo
dc.creatorI. C.; Simabuco
dc.creatorF. M.; Donato
dc.creatorJ.
dc.creatorJr.; Bittencourt
dc.creatorJ. C.; Lopes-Cendes
dc.creatorI.; Prada
dc.creatorP. O.
dc.date2017
dc.datefev
dc.date2017-11-13T13:56:34Z
dc.date2017-11-13T13:56:34Z
dc.date.accessioned2018-03-29T06:09:54Z
dc.date.available2018-03-29T06:09:54Z
dc.identifierInternational Journal Of Obesity. Nature Publishing Group, v. 41, p. 268 - 278, 2017.
dc.identifier0307-0565
dc.identifier1476-5497
dc.identifierWOS:000394143700010
dc.identifier10.1038/ijo.2016.174
dc.identifierhttp://www.nature.com/ijo/journal/v41/n2/full/ijo2016174a.html
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/329886
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1366911
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionTo investigate whether the Cdc2-like kinase 2 (CLK2) is expressed in hypothalamic neurons and if it is, whether the hypothalamic CLK2 has a role in the regulation of energy balance. SUBJECTS: Swiss mice on chow or high-fat diet (HFD) and db/db mice on chow diet were used to address the role of CLK2 in the hypothalamus. RESULTS: Hypothalamic CLK2(Thr343) phosphorylation, which induces CLK2 activity, is regulated in vivo by refeeding, insulin and leptin, in a PI3K (phosphoinositide 3-kinase)-dependent manner. The reduction of CLK2 expression in the hypothalamus, by chronic pharmacological inhibition with TG003 or by chronic knockdown with small interfering RNA was sufficient to abolish the anorexigenic effect of insulin and leptin, to increase body weight, fat mass, food intake and to decrease energy expenditure in mice on chow. In contrast, CLK2(Thr343) phosphorylation in the hypothalamus in response to insulin, leptin or refeeding was impaired in mice on HFD or in db/db mice. Chronic CLK2 inhibition in the hypothalamus was associated with a slight increase in the fasting blood glucose levels, reduction in PEPCK (phosphoenolpyruvate carboxykinase) expression in the liver and enhanced glucose production from pyruvate, suggesting a regulation of hepatic glucose production. Further, overexpressing CLK2 in the mediobasal hypothalami of mice on HFD or in db/db mice by adenovirus partially reversed the obese phenotype. CONCLUSIONS: Thus, our results suggest that protein CLK2 integrates some important hypothalamic pathways, and may be a promising molecule for new therapeutic approaches for obesity and diabetes.
dc.description41
dc.description2
dc.description268
dc.description278
dc.descriptionState University of Campinas (FUNCAMP)
dc.descriptionFAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo), Sao Paulo, Brazil [2012/10338-6, 2015/00343-0, CEPID 2013/07607-8]
dc.descriptionCNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [481084/2013-4]
dc.descriptionINCT (Instituto Nacional Ciencia e Tecnologia de Obesidade e Diabetes) [573856/2008-7]
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageEnglish
dc.publisherNature Publishing Group
dc.publisherLondon
dc.relationInternational Journal of Obesity
dc.rightsfechado
dc.sourceWOS
dc.subjectHepatic Glucose-production;food-intake;insulin Action;leptin;brain;inhibition;deficiency;metabolism;gene;clk2
dc.titleCdc2-like Kinase 2 In The Hypothalamus Is Necessary To Maintain Energy Homeostasis
dc.typeArtículos de revistas


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