Aerobic exercise training in wild type and CETP transgenic mice does not affect cellular cholesterol removal and expression of genes involved in lipid flux in macrophages and aortic arch

• Grant number: 11/15153-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2012
• End date: March 31, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marisa Passarelli
• Grantee: Paula Ramos Pinto
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Regular physical activity improves lipid and lipoprotein metabolism, decreasing the incidence of cardiovascular disease. Recent findings have shown that aerobic exercise physical training improves reverse cholesterol transport (RCT) in mice, which occurs by favoring the cholesterol traffic from macrophages through HDL to plasma, liver and feces. This event is associated with a higher expression of HDL hepatic receptors, such as SR-BI and ABCA-1, and also LDL receptor. In macrophages, however, there is not much information about the role of regular aerobic exercise on the modulation of cholesterol efflux, that characterizes the first step of RCT. Thus, the aim of this study is to evaluate the influence of aerobic exercise training in C57BL6 human CETP-transgenic mice in macrophage RCT. It will be determined in macrophage isolated from mice: ABCA-1, ABCG-1, SR-BI, LXRa, LXRb and PPARg mRNA expression; 2) the protein content of ABCA-1, ABCG-1, SR-BI, LXRa/b e PPARg; 3) 14C-cholesterol efflux, in different interval of time, mediated by apo A-I and HDL subfraction; and 4) the selective contribution of HDL receptors for cellular cholesterol removal. Mice will be trained on treadmill (15m/min; 30 min/day), during 6 weeks and a control group will be kept sedentary. Basal and final plasma cholesterol, triglycerides and CETP activity will be determined, as well as lipoprotein profile by FPLC and body weight. mRNA RCT-involved will be determined in trained and sedentary mice peritoneal macrophages by RT-PCR and, protein content by flow cytometry and imunoblot. Trained and sedentary mice peritoneal macrophages will be overloaded with acetylated LDL and 14C-cholesterol, followed incubation with cyclic AMP or ABCA-1 and SR-BI selective blockers. Cholesterol efflux will be determined in these cells after apo A-I, HDL2 or serum addition. Findings will be important to elucidate the influence of physical exercise in macrophage RCT in an animal model that resembles RCT in humans.

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)

PINTO, PAULA RAMOS; FERRARETTO MOURA ROCCO, DEBORA DIAS; OKUDA, LIGIA SHIMABUKURO; MACHADO-LIMA, ADRIANA; CASTILHO, GABRIELA; DA SILVA, KAROLLINE SANTANA; GOMES, DIEGO JUVENAL; PINTO, RAPHAEL DE SOUZA; IBORRA, RODRIGO TALLADA; FERREIRA, GUILHERME DA SILVA; et al. Aerobic exercise training enhances the in vivo cholesterol trafficking from macrophages to the liver independently of changes in the expression of genes involved in lipid flux in macrophages and aorta. LIPIDS IN HEALTH AND DISEASE, v. 14, SEP 16 2015. (12/19112-0, 11/04631-0, 12/12088-7, 11/15153-1, 12/04831-1, 12/18724-2, 13/02854-7)

PINTO, PAULA R.; DA SILVA, KAROLLINE S.; IBORRA, RODRIGO T.; OKUDA, LIGIA S.; GOMES-KJERULF, DIEGO; FERREIRA, GUILHERME S.; MACHADO-LIMA, ADRIANA; ROCCO, DEBORA D. F. M.; NAKANDAKARE, EDNA R.; MACHADO, UBIRATAN F.; et al. Exercise Training Favorably Modulates Gene and Protein Expression That Regulate Arterial Cholesterol Content in CETP Transgenic Mice. FRONTIERS IN PHYSIOLOGY, v. 9, MAY 8 2018. (12/19112-0, 16/15603-0, 13/11084-0, 12/12088-7, 11/15153-1, 12/18724-2, 13/02854-7, 14/07617-6, 15/21072-5)

DA SILVA, KAROLLINE S.; PINTO, PAULA R.; FABRE, NELLY T.; GOMES, DIEGO J.; THIEME, KARINA; OKUDA, LIGIA S.; IBORRA, RODRIGO T.; FREITAS, VANESSA G.; SHIMIZU, MARIA H. M.; TEODORO, WALCY R.; et al. N-acetylcysteine Counteracts Adipose Tissue Macrophage Infiltration and Insulin Resistance Elicited by Advanced Glycated Albumin in Healthy Rats. FRONTIERS IN PHYSIOLOGY, v. 8, SEP 22 2017. (16/15603-0, 12/12088-7, 11/15153-1, 12/04831-1, 12/18724-2, 14/17251-9, 13/02854-7)

Academic Publications

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

PINTO, Paula Ramos. Aerobic exercise training in wild type and CETP transgenic mice does not affect cellular cholesterol removal and expression of genes involved in lipid lipid flux in macrophages and aortic arch. 2015. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.