Exercise alters the mitochondrial proteostasis and induces the mitonuclear imbalance and UPRmt in the hypothalamus of mice

Author(s):Show less -

Braga, Renata R. ^[1] ; Crisol, Barbara M. ^[1] ; Bricola, Rafael S. ^[1] ; Sant'ana, Marcella R. ^[2] ; Nakandakari, Susana C. B. R. ^[2] ; Costa, Suleyma O. ^[3] ; Prada, Patricia O. ^[4] ; da Silva, Adelino S. R. ^[5] ; Moura, Leandro P. ^{[1, 6, 7]} ; Pauli, Jose R. ^{[1, 6]} ; Cintra, Dennys E. ^[2] ; Ropelle, Eduardo R. ^{[1, 6, 8, 9]}

Affiliation

^[1] Univ Campinas UNICAMP, Sch Appl Sci, Lab Mol Biol Exercise LaBMEx, BR-13484350 Limeira, SP - Brazil

^[2] Univ Estadual Campinas, Sch Appl Sci, Lab Nutr Genom LabGeN, BR-13484350 Limeira, SP - Brazil

^[3] Univ Estadual Campinas, Sch Appl Sci, Lab Metab Disorders, Campinas, SP - Brazil

^[4] Univ Campinas UNICAMP, Sch Appl Sci, Lab Mol Res Obes Labimo, BR-13484350 Limeira, SP - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Sch Phys Educ & Sport Ribeirao Preto, Postgrad Program Rehabil & Funct Performance, BR-14040900 Ribeirao Preto, SP - Brazil

^[6] Univ Campinas UNICAMP, CEPECE Ctr Res Sport Sci, Sch Appl Sci, BR-13484350 Limeira, SP - Brazil

^[7] Univ Campinas UNICAMP, Sch Appl Sci, Exercise Cell Biol Lab ECeBiL, BR-13484350 Limeira, SP - Brazil

^[8] Univ Campinas UNICAMP, Fac Med Sci, Dept Internal Med, BR-13083872 Campinas, SP - Brazil

^[9] Univ Estadual Campinas, Obes & Comorbid Res Ctr OCRC, Sao Paulo - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 FEB 15 2021.
• Web of Science Citations: 0

Abstract

The maintenance of mitochondrial activity in hypothalamic neurons is determinant to the control of energy homeostasis in mammals. Disturbs in the mitochondrial proteostasis can trigger the mitonuclear imbalance and mitochondrial unfolded protein response (UPRmt) to guarantee the mitochondrial integrity and function. However, the role of mitonuclear imbalance and UPRmt in hypothalamic cells are unclear. Combining the transcriptomic analyses from BXD mice database and in vivo experiments, we demonstrated that physical training alters the mitochondrial proteostasis in the hypothalamus of C57BL/6J mice. This physical training elicited the mitonuclear protein imbalance, increasing the mtCO-1/Atp5a ratio, which was accompanied by high levels of UPRmt markers in the hypothalamus. Also, physical training increased the maximum mitochondrial respiratory capacity in the brain. Interestingly, the transcriptomic analysis across several strains of the isogenic BXD mice revealed that hypothalamic mitochondrial DNA-encoded genes were negatively correlated with body weight and several genes related to the orexigenic response. As expected, physical training reduced body weight and food intake. Interestingly, we found an abundance of mt-CO1, a mitochondrial DNA-encoded protein, in NPY-producing neurons in the lateral hypothalamus nucleus of exercised mice. Collectively, our data demonstrated that physical training altered the mitochondrial proteostasis and induced the mitonuclear protein imbalance and UPRmt in hypothalamic cells. (AU)

• FAPESP's process: 17/18695-6 - Effects of nicotinamide Riboside supplementation and aerobic training on mitonuclear imbalance and on mitochondrial UPR in the hypothalamus of mice
• Grantee: Renata Rosseto Braga
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/07634-9 - Evaluation of mitonuclear imbalance and UPRmt in the skeletal muscle of exercise mice: The role JNK and PKR.
• Grantee: Eduardo Rochete Ropelle
• Support Opportunities: Regular Research Grants
• 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