title: Maraviroc ameliorates the increased adipose tissue macrophage recruitment induced by a high-fat diet in a mouse model of obesity.
abstract: BACKGROUND
  Any strategy designed to decrease the macrophage content in adipose tissue (AT) is of great value as a way to decrease inflammation in this fat depot and also as a way to prevent or treat obesity and associated disorders. Maraviroc (MVC), a CCR5 antagonist approved for the treatment of HIV-infected patients, has beneficial effects on metabolism. The objective of this study was to investigate the effects of MVC on AT macrophage recruitment in a mouse model of obesity. The plausible underlying mechanisms of action were also investigated.
  
  
  METHODS
  32 male C57BL/6 mice were randomly assigned to the following groups: control, MVC (300 mg/l MVC in drinking water), high-fat diet (HFD) or HFD+MVC. After 16 weeks of treatment, histopathological and molecular analyses were performed on epididymal fat.
  
  
  RESULTS
  Our results demonstrated that MVC reduced the presence of macrophages in epididymal fat despite the ingestion of an HFD. The inhibition of MCP-1 gene expression and JNK signalling pathway along with the upregulation of protective cytokines such as cardiotrophin-1 could contribute to these actions. MVC effects on AT macrophage recruitment were associated with a lower body weight gain and a partial improvement in insulin resistance despite an HFD.
  
  
  CONCLUSIONS
  We have demonstrated the ability of MVC to ameliorate the increased AT macrophage recruitment induced by an HFD in a mouse model of obesity. These actions could be of interest when designing antiretroviral treatments in HIV-patients.
authors.affiliation: Infectious Diseases Department, Center for Biomedical Research of La Rioja, Hospital San Pedro, Logroño, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Matute
authors.affiliation: Lung Cancer Unit, Center for Biomedical Research of La Rioja, Logroño, Spain.
authors.forename: José G
authors.initials: JG
authors.lastname: Pichel
authors.affiliation: Genomics Core Facility, Center for Biomedical Research of La Rioja, Logroño, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Iñiguez
authors.affiliation: Infectious Diseases Department, Center for Biomedical Research of La Rioja, Hospital San Pedro, Logroño, Spain.
authors.forename: Emma
authors.initials: E
authors.lastname: Recio-Fernández
authors.affiliation: Infectious Diseases Department, Center for Biomedical Research of La Rioja, Hospital San Pedro, Logroño, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Pérez-Martínez
authors.affiliation: Lung Cancer Unit, Center for Biomedical Research of La Rioja, Logroño, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Torrens
authors.affiliation: Infectious Diseases Department, Center for Biomedical Research of La Rioja, Hospital San Pedro, Logroño, Spain.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Blanco
authors.affiliation: Infectious Diseases Department, Center for Biomedical Research of La Rioja, Hospital San Pedro, Logroño, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Oteo
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003510:Cyclohexanes / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D000077592:Maraviroc; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D014230:Triazoles / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D003510:Cyclohexanes; D016207:Cytokines; D014230:Triazoles; C092073:cardiotrophin 1; D048670:MAP Kinase Kinase 4; D000077592:Maraviroc