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Effects of different exercise intensities on clusterin metabolism and its interference on insulin signaling in rodents

Grant number: 16/12569-6
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): December 01, 2016
Status:Discontinued
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Leandro Pereira de Moura
Grantee:Rodrigo Martins Pereira
Home 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):19/04457-1 - Short-term aerobic physical exercise and hepatic metabolism: the role of ApoJ, BE.EP.DD

Abstract

Clusterin, or apolipoprotein J (Apo B) through its membrane receptor (LRP2) acts on insulin signaling pathway potentiating its effects on peripheral tissues (skeletal muscle, liver and adipose tissue) and also the hypothalamus. These findings have been described as physiological data, however as pilot data already brought all the insulin signaling pathway in liver clusterin knockouts mice liver and we found that when there is a deletion of clusterin in the liver the phosphorilation of key proteins responsible for insulin signlaing transduction is decreased, resulting in increased of insulin resistance in the liver. Therefore, from these results we initially suggest the liver as an important secretory organ of clusterin and also its important role in the insulin signaling (see pilot data). However, the expression of this protein in peripheral tissues and its mechanisms of action are not fully understood. It is known that physical exercise is able to regulate crucial proteins involved in insulin signaling and promotes metabolic improvements in diabetic animals and humans. However, its effects in the regulation of clusterin and hence glucose homeostasis have not been elucidated. Therefore, this research proposal aims to initially know the metabolism of clusterin throughout the day and evaluate the nutritional effect of the organism in clusterin secretion and also assess the circadian cycle of this apoprotein (secretion over 24hrs with analyzes in each 2 hours). Later, we will evaluate its role in insulin signaling in the liver of lean and obese animals subjected to different exercise protocols (moderate and heavy intensities) and trying to understand its mechanistic we will do a silencing of LRP2 in the liver and try to elucidate how occurs this cross-talk between clusterin and insulin pathways. (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)
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; CINTRA, DENNYS ESPER; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO; DE MOURA, LEANDRO PEREIRA. Short-term strength training reduces gluconeogenesis and NAFLD in obese mice. Journal of Endocrinology, v. 241, n. 1, p. 59-70, APR 2019. Web of Science Citations: 1.
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. Web of Science Citations: 6.
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. Web of Science Citations: 17.

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