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Study of Clk2 regulation in hypothalamus of obese mice

Grant number: 12/10058-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2012
Effective date (End): August 31, 2017
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Patrícia de Oliveira Prada
Grantee:Paula Gabriele Fernandes Quaresma Bergonsi
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):15/16561-7 - The role of neuronal Cdc-2-Like kinase 2 (Clk2) in the modulation of energy balance, BE.EP.DR

Abstract

Obesity is a disease of worldwide increasing prevalence. Therefore, the study of molecular mecanisms that induce obesity is crucial. The hypothalamus and its nuclei coordinate the balance between food intake and energy expenditure through metabolic, neural and hormonal signs. Insulin and leptin act in hypothalamus and assist in control of energy balance. Cdc2-like protein (Clk2) is regulated in liver by refed and is phosphorylated in response to insulin stimuli in this tissue. However, it is not known whether this regulation occurs in hypothalamus. Thus, our objectives are 1) investigate the expression of Clk2 in hypothalamic nuclei through immunofluorescence; investigate whether refed, insulin or leptin increase Clk2 phosphorylation in hypothalamic nuclei and, whether this modulation is dependent of PI3K/Akt pathway. In addiction, 2) investigate whether reduction, by pharmacological inhibitor or siRNA, or the over-expression of Clk2 by adenovirus, change body weight, food intake, respiratory exchange rate, espontaneous activity, neuropeptides expression, fast glycemia and endogenous glucose production. Diet induced obesity is associated with insulin and leptin resistance in hypothalamus. Accordingly, our objective is to 3)investigate Clk2 phosphorylaton/expression modulation induced by insulin and leptin in obese mice.

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BERGONSI, Paula Gabriele Fernandes Quaresma. Hypothalamic CLK2 is important for energy homeostasis. 2017. Doctoral Thesis - Universidade Estadual de Campinas, Faculdade de Ciências Médicas.

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