The role of physical exercise in pathways signaling of clusterin/leptin in hypothalamus of obese mice

• Grant number: 16/24406-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): May 01, 2017
• Effective date (End): June 30, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Effort
• Principal Investigator: Leandro Pereira de Moura
• Grantee: Kellen Cristina da Cruz Rodrigues
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated research grant: 15/07199-2 - Role of clusterin/ApoJ on insulin signalling in response to physical exercise in rodents and humans, AP.JP
• Associated scholarship(s): 19/19938-5 - Short-term aerobic physical exercise and ApoJ action: the interorgan communications between liver and hypothalamus, BE.EP.DD

Abstract

Obesity is a major problem of public health in many countries and its main characteristic is given by the exaggerated accumulation of fat causing harmful effects in different tissues in organism. Nowadays, the epidemic effects affects a growing number of people harming the parameters of heath, quality of life, and thus causing important economic and development losses of many contemporary societies. In the center of attention and with prominent role in maintaining energy homeostasis, the hypothalamus is the structure from central nervous system responsible for the control of food intake and energy expenditure through its coordinated communication between neurons. However, experimental studies have shown that in obesity, hypothalamic neurons show impairment in leptin signaling and another biomolecules that have crucial effects on energy homeostasis. The binding of leptin its membrane receptor (LepRb) in hypothalamic neurons promotes the phosphorylation of Janus kinase 2 (JAK-2) and STAT-3 (signal transducer and activator of transcription 3), inducing the synthesis of pro-opiomelanocortin (POMC) that produces the anorexigenic peptide alpha melanocyte stimulating (±-MSH) and cocaine-and amphetamine-regulated transcript (CART), important peptides responsible for regulating of food intake and satiety. The glycoprotein clusterin/apoliprotein and its receptor LRP2 has received enough attention from researchers because it has a role as co-regulator of leptin signaling in the hypothalamus and promotes phosphorylation of JAK-2 and subsequently of increased POMC. Therefore, factors capable of regulating the leptin and clusterin pathways may be promising in the fight against obesity. Among non-pharmacological interventions, physical exercise demonstrated be able to increase sensitivity of leptin in the hypothalamus attenuating the hyperphagia in obese animals induced by diet rich in saturated fat. This positive effects caused by exercise involves the reduction of biomolecules related the low-grade inflammatory process and stress of endoplasmic reticulum that impair signaling of leptin in the hypothalamus. However, the effects of physical exercise on leptin/clusterin signaling are unknown. Thus, whether the physical exercise enhances the interaction of clusterin and leptin pathways in hypothalamus, the regulation of this signaling pathway may become a potential therapeutic target for obesity. Then, the aim of this study is investigate the role of physical exercise on clusterin/leptin signaling in hypothalamus of obese mice. (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)

DA CRUZ RODRIGUES, KELLEN C.; PEREIRA, RODRIGO M.; DE CAMPOS, THAIS D. P.; DE MOURA, RODRIGO F.; DA SILVA, ADELINO S. R.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; PAULI, JOSE R.; DE ARAUJO, MICHEL B.; DE MOURA, LEANDRO P.. The Role of Physical Exercise to Improve the Browning of White Adipose Tissue via POMC Neurons. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 12, MAR 28 2018. (15/07199-2, 16/24406-4)

PEREIRA, RODRIGO MARTINS; DA CRUZ RODRIGUES, KELLEN CRISTINA; SANT'ANA, MARCELLA RAMOS; PERUCA, GUILHERME FRANCISCO; MORELLI, ANA PAULA; SIMABUCO, FERNANDO M.; DA SILVA, ADELINO S. R.; CINTRA, DENNYS ESPER; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO; et al. Strength exercise reduces hepatic pyruvate carboxylase and gluconeogenesis in DIO mice. Journal of Endocrinology, v. 247, n. 2, p. 127-138, NOV 2020. (16/12569-6, 15/07199-2, 16/24406-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RODRIGUES, Kellen Cristina da Cruz. O papel da apolipoproteína J mediada pela micróglia e pelo exercício no metabolismo glicolítico e na sensibilidade à insulina em camundongos obesos induzidos por dieta. 2022. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas Limeira, SP.