Implications of interleukin-6 on UPRmt in the hypothalamus of obese mice

• Grant number: 21/04292-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2021
• End date: May 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Eduardo Rochete Ropelle
• Grantee: Carlos Kiyoshi Katashima
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated research grant: 19/21709-4 - Implications of mitonuclear imbalance and UPRmt in hypothalamic neurons in the genesis of Obesity, AP.TEM

Abstract

Mitochondrial activity in hypothalamic neurons plays a critical role in the control of food intake and energy homeostasis. The consumption of high fat diet can promote deleterious signals, altering proteostasis and mitochondrial activity. In response to different types of cellular stress, mitochondria activate a mechanism known as mitochondrial Unfolded Protein Response (UPRmt) to maintain or restore the mitochondrial proteostasis and activity. Studies have reported that interleukin-6 (IL-6) can stimulate mitochondrial biogenesis and activity in several stress conditions, however, the role of IL-6 onthe UPR mt is not completely understood. Thus, the aim of this project is to to investigate the role of IL-6 on UPRmt in hypothalamus of obese rodents. For the development of this project, experiments will be combined involving in vivo genetic modification (rAAV, and knockout animals), pharmacological treatments by using intrecebroventricular (ICV) micro injections and physical exercise in high-fat diet fed mice. Hypothalamic nuclei dissection will be combined to, immunofluorescence, assessment of mitochondrial respiration, bioinformatics analysis, and others. We are convencing that the development the current project may contribute to the advancement of knowledge about the effects of IL-6 on UPRmt in populations of hypothalamic neurons, as well as in the relationship of this mechanism to the development of the obese phenotype. (AU)

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)

DE ANDRADE JUNIOR, SCYLAS JOSE; ROCHA, MATHEUS BISCARO; KATASHIMA, CARLOS KIYOSHI. Examining the implications of glutathione peroxidase 4 overexpression and its impact on sarcopenia phenotypes in mice. JOURNAL OF PHYSIOLOGY-LONDON, v. 602, n. 5, p. 2-pg., 2024-02-03. (23/04659-9, 21/04292-2)

CARNEIRO, FERNANDA S.; KATASHIMA, CARLOS K.; DODGE, JOSHUA D.; CINTRA, DENNYS E.; PAULI, JOSE RODRIGO; DA SILVA, ADELINO S. R.; ROPELLE, EDUARDO R.. Tissue-specific roles of mitochondrial unfolded protein response during obesity. Obesity Reviews, v. 25, n. 9, p. 15-pg., 2024-06-16. (22/02350-8, 21/04292-2, 19/21709-4)