Role of clusterin/ApoJ on insulin signalling in response to physical exercise in rodents and humans

• Grant number: 15/07199-2
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: October 01, 2016
• End date: February 28, 2021
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Leandro Pereira de Moura
• Grantee: Leandro Pereira de Moura
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated research grant(s): 18/04932-9 - Meta-analysis and physical activity patterns and weight changes in premenopausal women: findings and methods, AV.EXT
• Associated scholarship(s): 20/04878-4 - Could exercise improve retinal function? Effects of different physical training protocols on clusterin/ApoJ metabolism in retinal in aged mice, BP.DR; 18/06833-8 - Could physical exercise improve visual acuity? Effects of different physical training protocols on tear composition and clusterin/ApoJ metabolism in the retina of obese rodent, BP.MS; 16/14388-9 - Comparison of two exercise protocols on action mechanism of clusterin/ApoJ in lean and obese mice, BP.DR; 16/24406-4 - The role of physical exercise in pathways signaling of clusterin/leptin in hypothalamus of obese mice, BP.DD; 16/12569-6 - Effects of different exercise intensities on clusterin metabolism and its interference on insulin signaling in rodents, BP.DD

Abstract

Insulin is an anabolic hormone with fundamental actions in organs and tissues to maintain body homeostasis. Abnormalities in insulin action to stimulate glucose uptake in skeletal muscle and inhibit hepatic glucose production, are usually found in individuals with insulin resistance and antecedent the development of type 2 diabetes mellitus (DM2). The hypertrophied adipose tissue releases several biomolecules such as hormones and pro-inflammatory cytokines and other factors that are involved in the induction of insulin resistance in obese. In this context, the knowledge in molecular biology with other fields of study have been trying to guide which factors are most important in the prevention and treatment of DM2. Clusterin, or apolipoprotein J (ApoJ) via its membrane receptor (LRP2) acts in the insulin signaling potentiating its effects on peripheral tissues (skeletal muscle, liver and adipose) and also in the hypothalamus. However, the expression of this protein in peripheral tissues and its mechanisms of action are not fully understood. Physical exercise is also able to regulate crucial proteins involved in insulin signaling and promote metabolic improvements in animal and human diabetics. However, its effects in the regulation of clusterin and consequently in glucose homeostasis have not been elucidated so far. Thus, understanding the molecular mechanisms involved in the action of clusterin in insulin signaling in the liver and muscle tissues in the exercise condition becomes essential for discovery of new therapeutic mechanisms, as well as for more effective prescription of physical exercise and safe for individuals affected by obesity and DM2. (AU)

Scientific publications

(11)

(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)

PEREIRA, RODRIGO M.; DA CRUZ RODRIGUES, KELLEN C.; SANT'ANA, MARCELLA R.; DA ROCHA, ALISSON L.; MORELLI, ANA P.; VERAS, ALLICE S. C.; GASPAR, RODRIGO S.; DA COSTA FERNANDES, CELIO J.; TEIXEIRA, GIOVANA R.; SIMABUCO, FERNANDO M.; et al. FOXO1 is downregulated in obese mice subjected to short-term strength training. Journal of Cellular Physiology, v. 237, n. 11, p. 13-pg., 2022-09-20. (16/12569-6, 15/07199-2)

DE MELO, DIEGO GOMES; ANARUMA, CHADI PELLEGRINI; DA CRUZ RODRIGUES, KELLEN CRISTINA; PEREIRA, RODRIGO MARTINS; PEREIRA DE CAMPOS, THAIS DANTIS; CANCIGLIERI, RAPHAEL SANTOS; RAMOS, CAMILA OLIVEIRA; CINTRA, DENNYS ESPER; ROPELLE, EDUARDO ROCHETE; RAMOS DA SILVA, ADELINO SANCHEZ; et al. Strength training alters the tissue fatty acids profile and slightly improves the thermogenic pathway in the adipose tissue of obese mice. SCIENTIFIC REPORTS, v. 12, n. 1, p. 14-pg., 2022-04-28. (15/07199-2)

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; ANARUMA, CHADI PELLEGRINI; SANT'ANA, MARCELLA RAMOS; PEREIRA DE CAMPOS, THAIS DANTIS; GASPAR, RODRIGO STELIZER; CANCIGLIERI, RAPHAEL DOS SANTOS; DE MELO, DIEGO GOMES; MEKARY, RANIA A.; RAMOS DA SILVA, ADELINO SANCHEZ; et al. Short-term strength training reduces gluconeogenesis and NAFLD in obese mice. Journal of Endocrinology, v. 241, n. 1, p. 59-70, APR 2019. (15/07199-2, 16/12569-6)

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)

DA CRUZ RODRIGUES, KELLEN CRISTINA; PEREIRA, RODRIGO MARTINS; PERUCA, GUILHERME FRANCISCO; TORRES BARBOSA, LUCAS WESLEY; SANT'ANA, MARCELLA RAMOS; MUNOZ, VITOR ROSETTO; MORELLI, ANA PAULA; SIMABUCO, FERNANDO MOREIRA; RAMOS DA SILVA, ADELINO SANCHEZ; CINTRA, DENNYS ESPER; et al. Short-Term Strength Exercise Reduces Hepatic Insulin Resistance in Obese Mice by Reducing PTP1B Content, Regardless of Changes in Body Weight. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 12, JUN 2021. (16/12569-6, 15/07199-2)

DE CAMPOS, THAIS DANTIS PEREIRA; DA CRUZ RODRIGUES, KELLEN CRISTINA; PEREIRA, RODRIGO MARTINS; ANARUMA, CHADI PELLEGRINI; DOS SANTOS CANCIGLIERI, RAPHAEL; DE MELO, DIEGO GOMES; DA SILVA, ADELINO SANCHEZ RAMOS; CINTRA, DENNYS ESPER; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO; et al. The protective roles of clusterin in ocular diseases caused by obesity and diabetes mellitus type 2. MOLECULAR BIOLOGY REPORTS, v. 48, n. 5, p. 4637-4645, MAY 2021. (18/06833-8, 15/07199-2)

PEREIRA DE CAMPOS, THAIS DANTIS; DA CRUZ RODRIGUES, KELLEN CRISTINA; PEREIRA, RODRIGO MARTINS; MORELLI, ANA PAULA; DA ROCHA, ALISSON LUIZ; CANCIGLIERI, RAPHAEL DOS SANTOS; RAMOS DA SILVA, ADELINO SANCHEZ; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO; SIMABUCO, FERNANDO MOREIRA; et al. Short-Term Combined Exercise Improves Inflammatory Profile in the Retina of Obese Mice. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 17, SEP 2020. (15/07199-2, 18/06833-8)

PEREIRA, RODRIGO MARTINS; BOTEZELLI, JOSE DIEGO; DA CRUZ RODRIGUES, KELLEN CRISTINA; MEKARY, RANIA A.; CINTRA, DENNYS ESPER; PAULI, JOSE RODRIGO; RAMOS DA SILVA, ADELINO SANCHEZ; ROPELLE, EDUARDO ROCHETE; DE MOURA, LEANDRO PEREIRA. Fructose Consumption in the Development of Obesity and the Effects of Different Protocols of Physical Exercise on the Hepatic Metabolism. NUTRIENTS, v. 9, n. 4, APR 2017. (15/07199-2, 16/12569-6)

PEREIRA, RODRIGO MARTINS; MEKARY, RANIA A.; DA CRUZ RODRIGUES, KELLEN CRISTINA; ANARUMA, CHADI PELLEGRINI; ROPELLE, EDUARDO ROCHETE; RAMOS DA SILVA, ADELINO SANCHEZ; CINTRA, DENNYS ESPER; PAULI, JOSE RODRIGO; DE MOURA, LEANDRO PEREIRA. Protective molecular mechanisms of clusterin against apoptosis in cardiomyocytes. HEART FAILURE REVIEWS, v. 23, n. 1, p. 123-129, JAN 2018. (15/07199-2, 16/12569-6)

ANARUMA, CHADI PELLEGRINI; PEREIRA, RODRIGO MARTINS; DA CRUZ RODRIGUES, KELLEN CRISTINA; RAMOS DA SILVA, ADELINO SANCHEZ; CINTRA, DENNYS ESPER; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO; DE MOURA, LEANDRO PEREIRA. Rock protein as cardiac hypertrophy modulator in obesity and physical exercise. Life Sciences, v. 254, AUG 1 2020. (18/15461-7, 16/14388-9, 15/07199-2)