Intermittent fasting combined with exercise training reduces body mass and alleviates hypothalamic disorders induced by high-fat diet intake

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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. ; Ropelle, Eduardo R. ; de Moura, Leandro P. ; Pauli, Jose R. ; de Freitas, Ellen C. ; Rorato, Rodrigo ; da Silva, Adelino Sanchez R.

• Document type: Journal article
• Source: JOURNAL OF NUTRITIONAL BIOCHEMISTRY; v. 119, p. 12-pg., 2023-05-29.

Abstract

High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hy-pothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF = HF diet mice submitted to IF; HF-T = HF diet mice sub-mitted to ET; HF-IFT = HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 ex-pression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei.& COPY; 2023 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 16/17968-6 - Hypothalamic neuronal circuitry and phenotypes involved in the coupling of hypothalamic-pituitary-adrenal axis activity to changes in the energy homeostasis
• Grantee: Rodrigo César Rorato
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/08192-0 - Autophagy responses in the hypothalamus of obese mice submitted to intermittent fasting associated with physical training
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/17532-1 - Physical exercise as a non-pharmacological strategy in the prevention and treatment of Alzheimer's Disease
• Grantee: Gustavo Paroschi Morais
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/25492-4 - Effects of the combination of intermittent fasting with physical exercise on the hypothalamic autophagy pathway in obese mice
• Grantee: Luciana da Costa Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/21709-4 - Implications of mitonuclear imbalance and UPRmt in hypothalamic neurons in the genesis of Obesity
• Grantee: Eduardo Rochete Ropelle
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/06291-3 - Multi-user Equipament approved in grant 2019/11820-5: ChemiDoc Imaging System and accessories
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Multi-user Equipment Program