Regulation of adipogenesis by lymphatic fluid stasis: Part II. Expression of adipose differentiation genes Journal Article

Authors: Aschen, S.; Zampell, J. C.; Elhadad, S.; Weitman, E.; De Brot, M.; Mehrara, B. J.
Article Title: Regulation of adipogenesis by lymphatic fluid stasis: Part II. Expression of adipose differentiation genes
Abstract: Background: Although fat deposition is a defining clinical characteristic of lymphedema, the cellular mechanisms that regulate this response remain unknown. The goal of this study was to determine how lymphatic fluid stasis regulates adipogenic gene activation and fat deposition. Methods: Adult female mice underwent tail lymphatic ablation and were euthanied at 1, 3, or 6 weeks postoperatively (n = 8 per group). Samples were analyzed by immunohistochemistry and Western blot analysis. An alternative group of mice underwent axillary dissections or sham incisions, and limb tissues were harvested 3 weeks postoperatively (n = 8 per group). Results: Lymphatic fluid stasis resulted in significant subcutaneous fat deposition and fibrosis in lymphedematous tail regions (p < 0.001). Western blot analysis demonstrated that proteins regulating adipose differentiation including CCAAT/enhancer-binding protein-α and adiponectin were markedly up-regulated in response to lymphatic fluid stasis in the tail and axillary models. Expression of these markers increased in edematous tissues according to the gradient of lymphatic stasis distal to the wound. Immunohistochemical analysis further demonstrated that adiponectin and peroxisome proliferator-activated receptor-γ, another critical adipogenic transcription factor, followed similar expression gradients. Finally, adiponectin and peroxisome proliferator-activated receptor-γ expression localized to a variety of cell types in newly formed subcutaneous fat. Conclusions: The mouse-tail model of lymphedema demonstrates pathologic findings similar to clinical lymphedema, including fat deposition and fibrosis. The authors show that lymphatic fluid stasis potently up-regulates the expression of fat differentiation markers both spatially and temporally. These studies elucidate mechanisms regulating abnormal fat deposition in lymphedema pathogenesis and therefore provide a basis for developing targeted treatments. © 2012 by the American Society of Plastic Surgeons.
Journal Title: Plastic and Reconstructive Surgery
Volume: 129
Issue: 4
ISSN: 0032-1052
Publisher: Lippincott Williams & Wilkins  
Date Published: 2012-04-01
Start Page: 838
End Page: 847
Language: English
DOI: 10.1097/PRS.0b013e3182450b47
PROVIDER: scopus
PUBMED: 22456356
PMCID: PMC3445411
Notes: --- - "Export Date: 1 May 2012" - "CODEN: PRSUA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Sonia Elhadad
    10 Elhadad
  2. Babak Mehrara
    293 Mehrara
  3. Jamie Christine Zampell
    29 Zampell
  4. Evan Scott Weitman
    18 Weitman
  5. Seth Aschen
    13 Aschen