Effects of physical training on inflammatory and apoptotic process in hypothalamic neurons of hungry control in high-fat diet-induced obese mice

• Grant number: 10/12091-2
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2011
• End date: July 31, 2013
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: José Rodrigo Pauli
• Grantee: José Rodrigo Pauli
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated researchers: Dennys Esper Corrêa Cintra ; Mario Jose Abdalla Saad

Abstract

Obesity results from an imbalance between caloric intake and energy expenditure. Changes in lifestyle, resulting in increased consumption of dietary fats and reduced physical activity have contributed to the worldwide obesity epidemic. The consumption of a high-fat diet activates the expression or the activity of inflammatory responsive proteins such as SOCS3, IKK, JNK, iNOS, TLR4 and PTP1B which impair leptin and insulin signaling in the hypothalamus, thus, disrupting the main satietogenic and adipostatic routes that maintain a stable body mass. In addition, new evidence showed that the high-fat diet activates hypothalamic IKK²/NF-ºB, at least in part, through elevated endoplasmic reticulum stress in the hypothalamus and that these phenomena are associated also with central insulin and leptin resistance, hyperphagia and body weight gain in animals. Recent research showed that consumption of dietary fats induces apoptosis of neurons and a reduction of synaptic inputs in the arcuate nucleus and lateral hypothalamus. Therefore, diet-induced hypothalamic apoptosis leads to an imbalance in orexigenic vs. anorexigenic neurons, and this favoring body mass gain in the diet-induced obese animals. On the order hand, physical activity is considered a cornerstone of the treatment for obesity. Exercise has long been reported to reduce body weight and visceral adiposity, increasing the energy expenditure and improving glycaemic control in overweight or diabetes type 2 patients. However, the effects of physical exercise in the inflammatory and apoptotic pathways in the hypothalamus remain unexplored. Thus, the main aim of the present study is to verify the role of effect of physical training to prevent the inflammation and apoptosis in hypothalamic cells of obese mice fed with a high-fat diet. For this, the obese mice fed to a high-fat diet will be submitted to physical training or acute exercise and will be evaluated weekly for variation in body weight and food intake. At the end of the experiment, the animals will be submitted to the insulin tolerance test. The content of the proteins IR², IRS-1, IRS-2, PI3q, Akt, JAK2, STAT3, FoxO1, JNK, IKK², IRS-1SER307, SOCS3, iNOS, TLR4, PERK, eIF2±, PARP, Bcl2, Bad, Bax, Caspase 9, FADD, POMC and NPY will be evaluated in the hypothalamus by immunoprecipitation and immunoblotting (AU)

Scientific publications

(4)

(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)

SOUZA PAULI, LUCIANA SANTOS; CHIARREOTTO ROPELLE, ELOIZE CRISTINA; DE SOUZA, CLAUDIO TEODORO; CINTRA, DENNYS ESPER; RAMOS DA SILVA, ADELINO SANCHEZ; RODRIGUES, BARBARA DE ALMEIDA; DE MOURA, LEANDRO PEREIRA; MARINHO, RODOLFO; DE OLIVEIRA, VANESSA; KATASHIMA, CARLOS KIYOSHI; et al. Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice. JOURNAL OF PHYSIOLOGY-LONDON, v. 592, n. 6, p. 1325-1340, MAR 15 2014. (11/14727-4, 11/13779-0, 10/12091-2)

DE MOURA, LEANDRO PEREIRA; SOUZA PAULI, LUCIANA SANTOS; CINTRA, DENNYS ESPER; DE SOUZA, CLAUDIO TEODORO; RAMOS DA SILVA, ADELINO SANCHEZ; MARINHO, RODOLFO; ROSTOM DE MELO, MARIA ALICE; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO. Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats. IMMUNITY & AGEING, v. 10, FEB 25 2013. (10/12091-2)

SOUZA PAULI, LUCIANA SANTOS; CHIARREOTTO ROPELLE, ELOIZE CRISTINA; DE SOUZA, CLAUDIO TEODORO; CINTRA, DENNYS ESPER; RAMOS DA SILVA, ADELINO SANCHEZ; RODRIGUES, BARBARA DE ALMEIDA; DE MOURA, LEANDRO PEREIRA; MARINHO, RODOLFO; DE OLIVEIRA, VANESSA; KATASHIMA, CARLOS KIYOSHI; et al. Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice (Publication with Expression of Concern. See vol. 594, pg. 5027, 2016) (Publication with Expression of Concern. See vol. 594, pg. 5027, 2016) (Publication with Expression of Concern. See vol. 594, pg. 5027, 2016). JOURNAL OF PHYSIOLOGY-LONDON, v. 592, n. 6, p. 16-pg., 2014-03-15. (10/12091-2, 11/14727-4, 11/13779-0)

CHIARREOTTO-ROPELLE, ELOIZE C.; PAULI, LUCIANA S. S.; KATASHIMA, CARLOS K.; PIMENTEL, GUSTAVO D.; PICARDI, PATY K.; SILVA, VAGNER R. R.; DE SOUZA, CLAUDIO T.; PRADA, PATRICIA O.; CINTRA, DENNYS E.; CARVALHEIRA, JOSE B. C.; et al. Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin and leptin signaling in obese rats. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 305, n. 5, p. E649-E659, SEP 2013. (11/14727-4, 11/13779-0, 10/12091-2)