title: Regulation of adipogenesis by lymphatic fluid stasis:  part I. Adipogenesis, fibrosis, and inflammation.
abstract: BACKGROUND
  Although fat deposition is a defining clinical characteristic of lymphedema, the cellular mechanisms that regulate this response remain unknown. The goals of this two-part study were to determine the effect of lymphatic fluid stasis on adipogenesis and inflammation (part I) and how these changes regulate the temporal and spatial expression of fat differentiation genes (part II).
  
  
  METHODS
  Adult female mice underwent tail lymphatic ablation and were euthanized 6 weeks after surgery (n = 20). Fat deposition, fibrosis, and inflammation were then analyzed in the regions of the tail exposed to lymphatic fluid stasis as compared with normal lymphatic flow.
  
  
  RESULTS
  Lymphatic fluid stasis in the tail resulted in significant subcutaneous fat deposition, with a 2-fold increase in fat thickness (p < 0.01). In addition, lymphatic stasis was associated with subcutaneous fat fibrosis and collagen deposition. Adipogenesis in response to lymphatic fluid stasis was associated with a marked mononuclear cell inflammatory response (5-fold increase in CD45 cells; p < 0.001). In addition, the authors noted a significant increase in the number of monocytes/macrophages as identified by F4/80 immunohistochemistry (p < 0.001).
  
  
  CONCLUSIONS
  The mouse-tail model has pathologic findings that are similar to clinical lymphedema, including fat deposition, fibrosis, and inflammation. Adipogenesis in response to lymphatic fluid stasis closely resembles this process in obesity. This model therefore provides an excellent means with which to study the molecular mechanisms that regulate the pathophysiology of lymphedema.
authors.affiliation: New York, N.Y. From the Divisions of Plastic and Reconstructive Surgery and Breast Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center.
authors.forename: Jamie C
authors.initials: JC
authors.lastname: Zampell
authors.forename: Seth
authors.initials: S
authors.lastname: Aschen
authors.forename: Evan S
authors.initials: ES
authors.lastname: Weitman
authors.forename: Alan
authors.initials: A
authors.lastname: Yan
authors.forename: Sonia
authors.initials: S
authors.lastname: Elhadad
authors.forename: Marina
authors.initials: M
authors.lastname: De Brot Andrade
authors.forename: Babak J
authors.initials: BJ
authors.lastname: Mehrara
mesh_terms: D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D024042:Collagen Type I / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D007150:Immunohistochemistry; D007249:Inflammation; D017493:Leukocyte Common Antigens / Q000032:analysis; D008196:Lymph / Q000502:physiology*; D008209:Lymphedema / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000503:physiopathology; D050151:Subcutaneous Fat / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D013623:Tail / Q000601:surgery
chemical_list: D000943:Antigens, Differentiation; D024042:Collagen Type I; C036763:monocyte-macrophage differentiation antigen; D017493:Leukocyte Common Antigens