Autophagy responses in the hypothalamus of obese mice submitted to intermittent fasting associated with physical training

• Grant number: 20/08192-0
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2020
• End date: January 31, 2023
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Adelino Sanchez Ramos da Silva
• Grantee: Adelino Sanchez Ramos da Silva
• Host Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Ellen Cristini de Freitas ; José Rodrigo Pauli

Abstract

The regulation of food intake and control of energy expenditure occur in the hypothalamus through orexigenic and anorexigenic neurons. Hypothalamic inflammation induced by obesity is associated with resistance to insulin and leptin, which impairs the actions of these hormones in the autophagy pathway, causing hyperphagia and increasing body adiposity. It is known that intermittent fasting modulates the expression of neuropeptides, promoting the reduction of body fat regardless of decreased calorie intake, in addition to increasing daily energy expenditure, which suggests a relationship between intermittent fasting and leptin and autophagy pathways in the hypothalamus. On the other hand, chronic physical exercise has a potent anti-inflammatory effect on hypothalamic tissue, being able to reestablish leptin signaling. However, the responses of the hypothalamic autophagic pathway in obese mice submitted to intermittent fasting associated with chronic physical exercise are unknown. Thus, the main objective of this research project will be to evaluate the effects of the association of intermittent fasting with chronic physical exercise in the pathways of inflammation, leptin, and autophagy in the hypothalamus of obese mice. Rodents will be divided into 5 groups: Lean control (C), Obese control (O), Intermittent fasting (JI), Trained (TR), and Trained who perform intermittent fasting (TRJ). Before and after the intermittent fasting and/or physical training protocols, caloric expenditure, body composition, insulin sensitivity, and serum levels of insulin and leptin will be assessed. Food intake and body weight will be assessed weekly. After rodent euthanasia, immunoblotting techniques for the analysis of the hypothalamic inflammatory pathway and central leptin response, real-time PCR for analysis of the expression of anorectic (POMC and CART) and orexigenic (NPY and AgRP) neuropeptides, and immunofluorescences for evaluating the expression of components of the autophagic pathway in the mid-basal portion of the hypothalamus will be used. For the comparison of results, parametric or non-parametric tests with a significance level of pd0.05 will be used. (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)

MACEDO, ANA PAULA AZEVEDO; DA SILVA, ADELINO SANCHEZ RAMOS; PAULI, JOSE RODRIGO. The muscle clock: how does muscle physiology change in 24 h in response to exercise?. JOURNAL OF PHYSIOLOGY-LONDON, v. 600, n. 4, p. 2-pg., 2021-07-12. (20/08192-0, 20/13443-1)

OLIVEIRA, LUCIANA DA COSTA; MORAIS, GUSTAVO PAROSCHI; DE OLIVEIRA, FRANCIANE PEREIRA; MATA, MILENE MONTAVONI; VERAS, ALLICE SANTOS CRUZ; DA ROCHA, ALISSON LUIZ; ELIAS, LUCILA LEICO KAGOHARA; TEIXEIRA, GIOVANA RAMPAZZO; DE MORAES, CAMILA; CINTRA, DENNYS E.; et al. Intermittent fasting combined with exercise training reduces body mass and alleviates hypothalamic disorders induced by high-fat diet intake. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 119, p. 12-pg., 2023-05-29. (16/17968-6, 20/08192-0, 19/17532-1, 17/25492-4, 19/21709-4, 21/06291-3)

OLIVEIRA, LUCIANA DA COSTA; MORAIS, GUSTAVO PAROSCHI; ROPELLE, EDUARDO R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; PAULI, JOSE R.; DE FREITAS, ELLEN C.; RORATO, RODRIGO; DA SILVA, ADELINO SANCHEZ R.. Using Intermittent Fasting as a Non-pharmacological Strategy to Alleviate Obesity-Induced Hypothalamic Molecular Pathway Disruption. FRONTIERS IN NUTRITION, v. 9, p. 15-pg., 2022-03-30. (17/25492-4, 20/08192-0)

AZEVEDO MACEDO, ANA PAULA; RAMOS DA SILVA, ADELINO SANCHEZ; MUNOZ, VITOR ROSETTO; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO. Mitochondrial dysfunction plays an essential role in remodeling aging adipose tissue. MECHANISMS OF AGEING AND DEVELOPMENT, v. 200, DEC 2021. (20/08192-0, 20/13443-1, 19/21709-4, 19/11820-5)