Please use this identifier to cite or link to this item:
Type: Artigo
Title: Cdc2-like Kinase 2 In The Hypothalamus Is Necessary To Maintain Energy Homeostasis
Author: Quaresma
P. G. F.; Weissmann
L.; Zanotto
T. M.; Santos
A. C.; de Matos
A. H. B.; Furigo
I. C.; Simabuco
F. M.; Donato
Jr.; Bittencourt
J. C.; Lopes-Cendes
I.; Prada
P. O.
Abstract: To 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.
Subject: Hepatic Glucose-production;food-intake;insulin Action;leptin;brain;inhibition;deficiency;metabolism;gene;clk2
Editor: Nature Publishing Group
Rights: fechado
Identifier DOI: 10.1038/ijo.2016.174
Date Issue: 2017
Appears in Collections:Unicamp - Artigos e Outros Documentos

Files in This Item:
File SizeFormat 
000394143700010.pdf1.48 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.