title: 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.
abstract: BACKGROUND
  Regular exercise prevents and regresses atherosclerosis by improving lipid metabolism and antioxidant defenses. Exercise ameliorates the reverse cholesterol transport (RCT), an antiatherogenic system that drives cholesterol from arterial macrophages to the liver for excretion into bile and feces. In this study we analyzed the role of aerobic exercise on the in vivo RCT and expression of genes and proteins involved in lipid flux and inflammation in peritoneal macrophages, aortic arch and liver from wild type mice.
  
  
  METHODS
  Twelve-week-old male mice were divided into sedentary and trained groups. Exercise training was performed in a treadmill (15 m/min, 30 min/day, 5 days/week). Plasma lipids were determined by enzymatic methods and lipoprotein profile by fast protein liquid chromatography. After intraperitoneal injection of J774-macrophages the RCT was assessed by measuring the recovery of (3)H-cholesterol in plasma, feces and liver. The expression of liver receptors was determined by immunoblot, macrophages and aortic mRNAs by qRT-PCR. (14)C-cholesterol efflux mediated by apo A-I and HDL2 and the uptake of (3)H-cholesteryl oleoyl ether ((3)H-COE)-acetylated-LDL were determined in macrophages isolated from sedentary and trained animals 48 h after the last exercise session.
  
  
  RESULTS
  Body weight, plasma lipids, lipoprotein profile, glucose and blood pressure were not modified by exercise training. A greater amount of (3)H-cholesterol was recovered in plasma (24 h and 48 h) and liver (48 h) from trained animals in comparison to sedentary. No difference was found in (3)H-cholesterol excreted in feces between trained and sedentary mice. The hepatic expression of scavenger receptor class B type I (SR-BI) and LDL receptor (B-E) was enhanced by exercise. We observed 2.8 and 1.7 fold rise, respectively, in LXR and Cyp7a mRNA in the liver of trained as compared to sedentary mice. Macrophage and aortic expression of genes involved in lipid efflux was not systematically changed by physical exercise. In agreement, (14)C-cholesterol efflux and uptake of (3)H-COE-acetylated-LDL by macrophages was similar between sedentary and trained animals.
  
  
  CONCLUSIONS
  Aerobic exercise in vivo accelerates the traffic of cholesterol from macrophages to the liver contributing to prevention and regression of atherosclerosis, independently of changes in macrophage and aorta gene expression.
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. paularamos@usp.br.
authors.forename: Paula Ramos
authors.initials: PR
authors.lastname: Pinto
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. drocco@unisanta.br.
authors.forename: Débora Dias Ferraretto Moura
authors.initials: DD
authors.lastname: Rocco
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. ligia.okuda@usp.br.
authors.forename: Ligia Shimabukuro
authors.initials: LS
authors.lastname: Okuda
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. adrianamachado@usp.br.
authors.forename: Adriana
authors.initials: A
authors.lastname: Machado-Lima
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. g.castilho@usp.br.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Castilho
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. kalsilva@usp.br.
authors.forename: Karolline Santana
authors.initials: KS
authors.lastname: da Silva
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. diego.djg@usp.br.
authors.forename: Diego Juvenal
authors.initials: DJ
authors.lastname: Gomes
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. rspinto@usp.br.
authors.forename: Raphael de Souza
authors.initials: Rde S
authors.lastname: Pinto
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. rtiborra@usp.br.
authors.forename: Rodrigo Tallada
authors.initials: RT
authors.lastname: Iborra
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. ferreira.gui@usp.br.
authors.forename: Guilherme da Silva
authors.initials: Gda S
authors.lastname: Ferreira
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. enakonda@usp.br.
authors.forename: Edna Regina
authors.initials: ER
authors.lastname: Nakandakare
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil. ubiratan@icb.usp.br.
authors.forename: Ubiratan Fabres
authors.initials: UF
authors.lastname: Machado
authors.affiliation: Laboratory of Endocrinology and Cellular Metabolism (LIM - 25), University of São Paulo Medical School, São Paulo, Brazil. malugia@lim25.fm.usp.br.
authors.forename: Maria Lucia Cardillo
authors.initials: ML
authors.lastname: Correa-Giannella
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. catanozi@usp.br.
authors.forename: Sergio
authors.initials: S
authors.lastname: Catanozi
authors.affiliation: Lipids Laboratory (LIM - 10), University of São Paulo Medical School, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil. mpassere@usp.br.
authors.forename: Marisa
authors.initials: M
authors.lastname: Passarelli
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism; D001692:Biological Transport; D001794:Blood Pressure; D001835:Body Weight; D002250:Carbon Radioisotopes; D002460:Cell Line; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D015870:Gene Expression; D007274:Injections, Intraperitoneal; D008099:Liver / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010805:Physical Conditioning, Animal; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D002250:Carbon Radioisotopes; D008076:Cholesterol, HDL; D011973:Receptors, LDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C023511:cholesteryl oleyl ether; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase