title: Increased density of sympathetic nerve fibers in metabolically activated fat tissue surrounding human synovium and mouse lymph nodes in arthritis.
abstract: OBJECTIVE
  To investigate the density of sympathetic nerve fibers in and the metabolic activation of fat tissue surrounding human synovium in rheumatoid arthritis (RA)/osteoarthritis (OA) and in the draining lymph nodes of arthritic and normal mice.
  
  
  METHODS
  Using immunofluorescence and immunohistochemistry, the density of sympathetic nerve fibers and the presence of nerve repellent factors were investigated. The metabolic activation of fat tissue was estimated by the occurrence of small-vacuole adipocytes, expression of β3-adrenoceptors, and adipose tissue weight.
  
  
  RESULTS
  The density of sympathetic nerve fibers was markedly increased in fat tissue surrounding RA synovium compared with that in fat tissue surrounding OA synovium. In adipose tissue adjacent to draining lymph nodes, the density of sympathetic nerve fibers was higher in arthritic mice compared with normal mice. In human synovium and mouse draining lymph nodes, the 2 sympathetic nerve repellent factors, semaphorin 3C and semaphorin 3F, were highly expressed. In arthritic compared with normal mice, the fat tissue around lymph nodes was markedly lighter, adipocytes had more fragmented lipid droplets, and fat tissue demonstrated high expression of β3-adrenoceptors.
  
  
  CONCLUSIONS
  This study demonstrated an increased density of sympathetic nerve fibers in metabolically activated fat tissue surrounding human RA synovium and the draining lymph nodes of arthritic mice. Because sympathetic neurotransmitters stimulate lipolysis, the repulsion of sympathetic nerve fibers from inflamed regions and their increased occurrence in fat tissue probably represent an adaptive program to support the proinflammatory process by releasing energy-rich substrates.
authors.affiliation: University Hospital Regensburg, Regensburg, Germany. rainer.straub@klinik.uni-regensburg.de
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
authors.forename: Torsten
authors.initials: T
authors.lastname: Lowin
authors.forename: Susanne
authors.initials: S
authors.lastname: Klatt
authors.forename: Christine
authors.initials: C
authors.lastname: Wolff
authors.forename: Luise
authors.initials: L
authors.lastname: Rauch
mesh_terms: D000273:Adipose Tissue / Q000294:innervation* / Q000378:metabolism / Q000473:pathology; D000320:Adrenergic Fibers / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000294:innervation* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D013583:Synovial Membrane / Q000294:innervation* / Q000378:metabolism / Q000473:pathology