title: Differential impact of obesity on the pathogenesis of RA or preclinical models is contingent on the disease status.
abstract: OBJECTIVE
  Studies were performed to uncover the significance of obesity in rheumatoid arthritis (RA) and preclinical models.
  
  
  METHODS
  Preclinical arthritis models were used to examine the impact of obesity on disease onset and remission. Conditioned media from RA adipose tissues were used to investigate the mechanism contributing to joint neutrophil influx and M1 macrophage differentiation observed in early and remission phases of arthritis.
  
  
  RESULTS
  We report that mice fed with high fat diet (HFD) have an earlier onset of collagen-induced arthritis (CIA) compared with mice on regular diet. However, the differences in CIA joint swelling between the two diet groups are lost once disease is established. We found that early arthritis triggered by obesity is due to elevated joint MIP2/interleukin-8 levels detected in CIA as well as in the RA and mouse adipose tissues and the effect of this chemokine on neutrophil recruitment. Although active disease progression is similarly affected in both diet groups, arthritis resolution is accelerated in lean mice while joint inflammation is sustained in obese mice. We document that HFD can prolong toll-like receptor (TLR)4-induced arthritis by increasing joint monocyte migration and further remodelling the recruited cells into M1 macrophages. Consistently, we show that adipose condition media can transform RA and wild-type naïve myeloid cells into M1 macrophages; however, this function is impaired by TLR4 blockade or deficiency.
  
  
  CONCLUSIONS
  We conclude that despite established disease being unaffected by obesity, the early and the resolution phases of RA are impacted by obesity through different mechanisms.
authors: Division of Rheumatology, Jesse Brown VA Medical Center, Chicago, Illinois, USA.|Division of Rheumatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: Seung-Jae
authors: SJ
authors: Kim
authors: Division of Rheumatology, Jesse Brown VA Medical Center, Chicago, Illinois, USA.|Division of Rheumatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: Zhenlong
authors: Z
authors: Chen
authors: Division of Rheumatology, Jesse Brown VA Medical Center, Chicago, Illinois, USA.|Division of Rheumatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: Abdul B
authors: AB
authors: Essani
authors: Division of Rheumatology, Jesse Brown VA Medical Center, Chicago, Illinois, USA.|Division of Rheumatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: Hatem A
authors: HA
authors: Elshabrawy
authors: Department of Microbiology & Immunology, Midwestern University, Downers Grove, Illinois, USA.
authors: Michael V
authors: MV
authors: Volin
authors: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: Giamila
authors: G
authors: Fantuzzi
authors: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors: Iain B
authors: IB
authors: McInnes
authors: Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA.|Division of Rheumatology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Joshua F
authors: JF
authors: Baker
authors: Division of Pulmonary, Division of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: Patricia
authors: P
authors: Finn
authors: Division of Cardiology, Division of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: George
authors: G
authors: Kondos
authors: Division of Rheumatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: Suncica
authors: S
authors: Volkov
authors: Division of Rheumatology, Jesse Brown VA Medical Center, Chicago, Illinois, USA.|Division of Rheumatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: William
authors: W
authors: Swedler
authors: Division of Rheumatology, Jesse Brown VA Medical Center, Chicago, Illinois, USA.|Division of Rheumatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: Shiva
authors: S
authors: Arami
authors: Division of Rheumatology, Jesse Brown VA Medical Center, Chicago, Illinois, USA.
authors: Nadera
authors: N
authors: Sweiss
authors: Division of Rheumatology, Jesse Brown VA Medical Center, Chicago, Illinois, USA.|Division of Rheumatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: Shiva
authors: S
authors: Shahrara
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D054426:Chemokine CXCL2 / Q000378:metabolism; D003094:Collagen; D016207:Cytokines / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D016209:Interleukin-8 / Q000378:metabolism; D007596:Joints / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009504:Neutrophils / Q000502:physiology; D009765:Obesity / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D054426:Chemokine CXCL2; D016207:Cytokines; D004041:Dietary Fats; D016209:Interleukin-8; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D003094:Collagen
keywords: Chemokines; Cytokines; Early Rheumatoid Arthritis; Inflammation; Rheumatoid Arthritis