title: High-Fat Diet-Induced Obesity Enhances Allograft Rejection.
abstract: Obesity promotes a state of low-grade inflammation that exacerbates chronic inflammatory diseases, such as asthma and inflammatory bowel disease. In transplantation, the survival of organs transplanted into obese patients is reduced compared with allografts in lean recipients. However, whether this is due to increased alloimmunity remains to be addressed conclusively.
  
  
  
  We used a mouse model of high-fat diet (HFD)-induced obesity and assessed immune responses to allogeneic stimulation in vitro, allogeneic splenocyte immunization in vivo, and allogeneic heart transplantation.
  
  
  
  Our results indicate that HFD altered the composition and phenotype of splenic antigen-presenting cells that led to their enhanced capacity to stimulate T cells. Immunization with allogeneic splenocytes in vivo resulted in increased alloreactivity, as determined by IFNγ production. Moreover, cardiac allograft rejection in HFD mice was modestly accelerated compared to aged-matched control animals fed a low-fat diet, correlating with enhanced alloreactive T cell function.
  
  
  
  Our results highlight the increased alloresponse triggered by HFD-induced obesity and its negative impact on transplant outcome.
authors.affiliation: 1 Department of Surgery, The University of Chicago, Chicago, IL. 2 Genentech, Inc., South San Francisco, CA. 3 Department of Medicine, The University of Chicago, Chicago, IL.
authors.forename: Luciana L
authors.initials: LL
authors.lastname: Molinero
authors.forename: Dengping
authors.initials: D
authors.lastname: Yin
authors.forename: Yuk Man
authors.initials: YM
authors.lastname: Lei
authors.forename: Luqiu
authors.initials: L
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Anita S
authors.initials: AS
authors.lastname: Chong
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Alegre
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006321:Heart / Q000502:physiology; D016027:Heart Transplantation; D007249:Inflammation; D007371:Interferon-gamma / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000276:immunology*; D010641:Phenotype; D012189:Retrospective Studies; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D007371:Interferon-gamma