Role of physical exercise in the regulation of MKP-3 protein in the hypothalamus of obese rats: effects on insulin signaling.

• Grant number: 13/25512-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2014
• End date: April 30, 2017
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: José Rodrigo Pauli
• Grantee: Barbara de Almeida Rodrigues
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

The inhibition of hungry is dependent on the presence of insulin and includes the participation of FoxO1 protein (transcription factor forkhead family BOX O). After stimulation with insulin, the protein Akt phosphorylates FoxO1, exporting it to the cytoplasma. Unlike in the absence of insulin, in which FoxO1 by Akt is not activated, its transcriptional activity in the nucleus of hypothalamic neurons is increased, resulting in increased expression of neuropeptide Y (NPY) and agouti-related protein (AgRP), both considered orexigenic neuropeptides. Admittedly, in cases of insulin resistance on hypothalamus the food intake is high, which can be explained by the drastic reduction in the activation of Akt and retention of FoxO1 in the cell nucleus. In this context, the protein MKP-3 (MAPK-phosphatase-3), significantly increased in the obese condition, has the ability to associate physically and dephosphorylation of the FoxO1 in neurons cells, resulting in increased hungry. Therefore, therapeutic actions capable of inhibiting the activity of MKP-3 in neurons cells of the hypothalamus can be revealed as protective agents against obesity and diabetes. Among non-pharmacological tools, the physical exercise has been shown to reduce inflammation and modulate the phosphorylation of Foxo1 in liver and hypothalamus of obese animals. However, it is still unknown effects of exercise on the MKP-3 protein in the central nervous system. These findings may contribute significantly to the understanding of the role of physical exercise in attenuating or reversing the disorders associated with food intake in obesity and diabetes, opening new perspectives for the treatment of these diseases. Therefore, the objective of this study is to assess the association FoxO1/MKP-3 and expression of MKP-3 in hypothalamic cells of hungry control of obese animals induced by high-fat diet submitted to acute exercise.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RODRIGUES, BARBARA DE A.; MUNOZ, VITOR R.; KUGA, GABRIEL K.; GASPAR, RAFAEL C.; NAKANDAKARI, SUSANA C. B. R.; CRISOL, BARBARA M.; BOTEZELLI, JOSE D.; PAULI, LUCIANA S. S.; DA SILVA, ADELINO S. R.; DE MOURA, LEANDRO P.; et al. Obesity Increases Mitogen-Activated Protein Kinase Phosphatase-3 Levels in the Hypothalamus of Mice. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 11, OCT 9 2017. (13/21491-2, 16/18488-8, 13/25512-4)

RODRIGUES, BARBARA DE ALMEIDA; KUGA, GABRIEL KEINE; MUNOZ, VITOR ROSETTO; GASPAR, RAFAEL CALAIS; TAVARES, MARIANA ROSOLEN; BOTEZELLI, JOSE DIEGO; RAMOS DA SILVA, ADELINO SANCHEZ; CINTRA, DENNYS ESPER; DE MOURA, LEANDRO PEREIRA; SIMABUCO, FERNANDO MOREIRA; et al. Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3)reduces FoxO1 phosphorylation in mice hypothalamus. Neuroscience Letters, v. 659, p. 14-17, OCT 17 2017. (16/18488-8, 13/25512-4)

RODRIGUES, BARBARA DE ALMEIRA; SOUZA PAULI, LUCIANA SANTOS; DE SOUZA, CLAUDIO TEODORO; RAMOS DA SILVA, ADELINO SANCHEZ; CORREA CINTRA, DENNYS ESPER; MARINHO, RODOLFO; DE MOURA, LEANDRO PEREIRA; CHIARREOTTO ROPELLE, ELOIZE CRISTINA; BOTEZELLI, JOSE DIEGO; ROPELLE, EDUARDO ROCHETE; et al. Acute Exercise Decreases Tribbles Homolog 3 Protein Levels in the Hypothalamus of Obese Rats. MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, v. 47, n. 8, p. 1613-1623, AUG 2015. (13/21491-2, 13/25512-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RODRIGUES, Barbara de Almeida. Role of physical exercise in the regulation of MKP-3 protein in hypothalamic of obese mammals: effects on insulin signaling. 2017. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas Limeira, SP.