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Effects of adipose tissue remodeling during cachexia in gastrointestinal cancer patients: potential role of TLR4 receptor during cachexia-induced browning of WAT

Grant number: 15/19259-0
Support type:Regular Research Grants
Duration: March 01, 2016 - February 28, 2018
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Miguel Luiz Batista Junior
Grantee:Miguel Luiz Batista Junior
Home Institution: Pró-Reitoria Acadêmica. Universidade de Mogi das Cruzes (UMC). Campus da Sede Mogi das Cruzes. Mogi das Cruzes , SP, Brazil

Abstract

Cachexia is a complex syndrome that affects multiple compartments and systems in cancer patients. White adipose tissue (WAT) loss is one of the most important clinical "markers" of such disease. Recently, some studies have shown morphological modifications (remodeling) in WAT, characterized by phenotypic changes of white adipocytes that became closer to brown adipocytes profile. This process has been described as browning of WAT. On the other hand, the most part of studies have just addressed some metabolic abnormalities, misevaluating tissue inflammation and, more important, the early events that result in morphological changes induced by cachexia. Moreover, considering the important role of innate immunity receptors as "connecting link" between inflammatory and metabolic events, to our knowledge, few or no studies have evaluated these relationships and their role during the different stages of cachexia. Thus, considering the role of Toll-like receptor 4 (TLR4) in controlling lipolysis, inflammation and consequent adipose tissue remodeling, it is reasonable to postulate that activation of these receptors would have an important role in remodeling of this tissue.Thus, we propose a translational study addressing the mechanisms involved in the early processes of WAT remodeling in cachexia. In addition, the process of metabolic dysfunction and consequent induction of the browning of WAT during the development of cachexia will be adressed in TLR4 knockout mice. In parallel, the same parameters will be evaluated in gastrointestinal cancer patients as well as a set of plasmatic markers and its possible diagnostic application. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Drug used to control cholesterol found effective against cancer-associated cachexia 
Articles published in other midia outlets (1 total):
Un fármaco que se aplica en el control del colesterol posee acción contra la caquexia asociada al cáncer 

Scientific publications (7)
(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)
GONCALVES, IVAN DE OLIVEIRA; BANDEIRA, ALEXANDRE NUNES; COELHO-JUNIOR, HELIO JOSE; AGUIAR, SAMUEL DA SILVA; CAMARGO, SAMUEL MINUCCI; ASANO, RICARDO YUKIO; BATISTA JUNIOR, MIGUEL LUIZ. Multicomponent Exercise on Physical Function, Cognition and Hemodynamic Parameters of Community-Dwelling Older Adults: A Quasi-Experimental Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, v. 16, n. 12 JUN 2 2019. Web of Science Citations: 0.
HENRIQUES, FELIPE; LOPES, MAGNO A.; FRANCO, FELIPE O.; KNOBL, PAMELA; SANTOS, KALTINAITIS B.; BUENO, LUANA L.; CORREA, VICTOR A.; BEDARD, ALEXANDER H.; GUILHERME, ADILSON; BIRBRAIR, ALEXANDER; PERES, SIDNEY B.; FARMER, STEPHEN R.; BATISTA, JR., MIGUEL L. Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling and Increases Survival in Cancer Cachexia Syndrome. SCIENTIFIC REPORTS, v. 8, DEC 21 2018. Web of Science Citations: 3.
LEAL, LUANA G.; LOPES, MAGNO A.; BATISTA, JR., MIGUEL L. Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases. FRONTIERS IN PHYSIOLOGY, v. 9, SEP 24 2018. Web of Science Citations: 24.
LOPES, MAGNO ALVES; FRANCO, FELIPE OLIVEIRA; HENRIQUES, FELIPE; PERES, SIDNEY BARNABE; BATISTA, JR., MIGUEL LUIZ. LLC tumor cells-derivated factors reduces adipogenesis in co-culture system. HELIYON, v. 4, n. 7 JUL 2018. Web of Science Citations: 0.
HENRIQUES, FELIPE SANTOS; LAURATO SERTIE, ROGERIO ANTONIO; FRANCO, FELIPE OLIVEIRA; KNOBL, PAMELA; NEVES, RODRIGO XAVIER; ANDREOTTI, SANDRA; LIMA, FABIO BESSA; GUILHERME, ADILSON; SEELAENDER, MARILIA; BATISTA, JR., MIGUEL LUIZ. Early suppression of adipocyte lipid turnover induces immunometabolic modulation in cancer cachexia syndrome. FASEB JOURNAL, v. 31, n. 5, p. 1976-1986, MAY 2017. Web of Science Citations: 5.
FRANCO, FELIPE DE OLIVEIRA; LOPES, MAGNO ALVES; HENRIQUES, FELIPE DOS SANTOS; DAS NEVES, RODRIGO XAVIER; BIANCHI FILHO, CESARIO; BATISTA, JR., MIGUEL LUIZ. Cancer cachexia differentially regulates visceral adipose tissue turnover. Journal of Endocrinology, v. 232, n. 3, p. 493-500, MAR 2017. Web of Science Citations: 4.
PREITE, NAILLIW Z.; DO NASCIMENTO, BRUNA P. P.; MULLER, CYNTHIA R.; AMERICO, ANNA LAURA V.; HIGA, TALITA S.; EVANGELISTA, FABIANA S.; LANCELLOTTI, CARMEN L.; HENRIQUES, FELIPE DOS SANTOS; BATISTA, JR., MIGUEL LUIZ; BIANCO, ANTONIO C.; RIBEIRO, MIRIAM O. Disruption of beta3 adrenergic receptor increases susceptibility to DIO in mouse. Journal of Endocrinology, v. 231, n. 3, p. 259-269, DEC 2016. Web of Science Citations: 8.

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