Exercise Training Favorably Modulates Gene and Protein Expression That Regulate Arterial Cholesterol Content in CETP Transgenic Mice

Author(s):Show less -

Pinto, Paula R. ^[1] ; da Silva, Karolline S. ^[1] ; Iborra, Rodrigo T. ^{[1, 2]} ; Okuda, Ligia S. ^[1] ; Gomes-Kjerulf, Diego ^[1] ; Ferreira, Guilherme S. ^[1] ; Machado-Lima, Adriana ^[3] ; Rocco, Debora D. F. M. ^[4] ; Nakandakare, Edna R. ^[1] ; Machado, Ubiratan F. ^[5] ; Correa-Giannella, Maria L. ^{[6, 7]} ; Catanozi, Sergio ^[1] ; Passarelli, Marisa ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Hosp Clin, Lab Lipides LIM 10, Sao Paulo - Brazil

^[2] Univ Sao Judas Tadeu, FCBS, Sao Paulo - Brazil

^[3] Univ Sao Judas Tadeu, Ciencias Envelhecimento, Sao Paulo - Brazil

^[4] Univ Santa Cecilia, Lab Fisiol Exercicio Fis & Saude, Fac Educ Fis & Esportes, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, Sao Paulo - Brazil

^[6] Univ Nove Julho, Programa posgrad Med, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Fac Med, Hosp Clin, Lab Carboidratos & Radioimunoensaio LIM 18, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN PHYSIOLOGY; v. 9, MAY 8 2018.
• Web of Science Citations: 3

Abstract

Aerobic exercise training (AET) improves the reverse cholesterol transport (RCT) in cholesteryl ester transfer protein-transgenic (CETP-tg) mice. We aimed at investigating the role of AET in the expression of genes and proteins involved in lipid flux in the aorta and macrophages of CETP-tg mice. Three-month-old male mice were randomly divided into trained (T; treadmill 15 m/min; 30 min/day) and sedentary (S) groups. After 6 weeks, peritoneal macrophages and the aortic arch were obtained immediately (0 h) or 48 h after the last exercise session. mRNA was determined by RT-qPCR, protein levels by immunoblot and C-14-cholesterol efflux determined in macrophages. AET did not change body weight, plasma cholesterol, triglycerides, glucose and CETP activity. In macrophages, at time 0 h, a higher expression of genes that encode PPAR gamma, ABCA-1 and a lower expression of MCP-1 and IL-10, was observed in T as compared to S. After 48 h, lower expressions of MCP-1 and PPAR gamma genes were observed in T mice. Increase in ABCA-1, SR-BI and IL-6 and decrease of LOX-1, MCP-1, TNF and IL-10 gene expression was observed in the aorta of T compared to S mice (0 h) and LOX-1 and MCP-1 remained diminished after 48 h. The protein level of MCP-1 and SR-BI in the aortic arch was unchanged in T animals after 48 h as compared to S, but LOX-1 was reduced confirming data of gene expression. The apo A-I and the HDL2 mediated-cholesterol efflux (8 and 24 h) were not different between T and S animals. In the presence of CETP, AET positively influences gene expression in the arterial wall and macrophages of CETP-tg mice contributing to the RCT and prevention of atherosclerosis. These changes were perceptible immediately after the exercise session and were influenced by the presence of CETP although independent of changes in its activity. Reductions in gene and protein expression of LOX-1 were parallel and reflect the ability of exercise training in reducing the uptake of modified LDL by the arterial wall macrophages. (AU)

• FAPESP's process: 12/19112-0 - Involvement of the RAGE/AGE axis in macrophage lipid accumulation induced by human advanced glycated albumin - contribution of glycemic control in diabetes mellitus.
• Grantee: Adriana Machado Saldiba de Lima
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 12/12088-7 - Glycemic control and the removal of macrophage cholesterol by ABCA-1: role of modified albumin by advanced glycation
• Grantee: Rodrigo Tallada Iborra
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 13/02854-7 - Anti-inflammatory role of apolipoprotein A-IV in diabetes mellitus and its impact on macrophage reverse cholesterol transport: influence of advanced glycation
• Grantee: Ligia Shimabukuro Okuda
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 14/07617-6 - Effect of aerobic exercise training in plasma and arterial distribution and concentration of oxysterols in dyslipidemic mice
• Grantee: Guilherme da Silva Ferreira
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 11/15153-1 - 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
• Grantee: Paula Ramos Pinto
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 13/11084-0 - Chronic sodium chloride restriction and atherogenesis in animal model of dyslipidemia and hypertension
• Grantee: Sergio Catanozi
• Support type: Regular Research Grants
• FAPESP's process: 12/18724-2 - Advanced glycated albumin and insulin resistance in rats: focus on periepididimal adipose tissue and N-acetylcysteine actions
• Grantee: Karolline Santana da Silva
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health
• Grantee: Ubiratan Fabres Machado
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 15/21072-5 - Influency of the glycemic control and nefropathy stage on the reverse cholesterol transport in Diabetes mellitus: role of metabolic memory induced by advanced glycated albumin
• Grantee: Marisa Passarelli
• Support type: Regular Research Grants