title: High-Fat Diet in the Absence of Obesity Does Not Aggravate Surgically Induced Lymphoedema in Mice.
abstract: BACKGROUND
  Lymphoedema represents the cardinal manifestation of lymphatic dysfunction and is associated with expansion of the adipose tissue in the affected limb. In mice, high-fat diet (HFD)-induced obesity was associated with impaired collecting lymphatic vessel function, and adiposity aggravated surgery-induced lymphoedema in a mouse model. The aim of the current study was to investigate whether adiposity is necessary to impair lymphatic function or whether increased lipid exposure alone might be sufficient in a surgical lymphoedema model.
  
  
  METHODS
  To investigate the role of increased lipid exposure in lymphoedema development we used a well-established mouse tail lymphoedema model. Female mice were subjected to a short-term (6 weeks) HFD, without development of obesity, before surgical induction of lymphedema. Lymphoedema was followed over a period of 6 weeks measuring oedema, evaluating tissue histology and lymphatic vascular function.
  
  
  RESULTS
  HFD increased baseline angiogenesis and average lymphatic vessel size in comparison to the chow control group. Upon induction of lymphedema, HFD-treated mice did not exhibit aggravated oedema and no morphological differences were observed in the blood and lymphatic vasculature. Importantly, the levels of fibro-adipose tissue deposition were comparable between the 2 groups and lymphatic vessel function was not impaired as a result of the HFD. Although the net immune cell infiltration was comparable, the HFD group displayed an increased infiltration of macrophages, which exhibited an M2 polarization phenotype.
  
  
  CONCLUSIONS
  These results indicate that increased adiposity rather than dietary influences determines predisposition to or severity of lymphedema.
authors.affiliation: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Epameinondas
authors.initials: E
authors.lastname: Gousopoulos
authors.forename: Sinem
authors.initials: S
authors.lastname: Karaman
authors.forename: Steven T
authors.initials: ST
authors.lastname: Proulx
authors.forename: Kristin
authors.initials: K
authors.lastname: Leu
authors.forename: Dorina
authors.initials: D
authors.lastname: Buschle
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
mesh_terms: D050154:Adiposity; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D008209:Lymphedema / Q000209:etiology*; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D011183:Postoperative Complications / Q000209:etiology*
keywords: High-fat diet; Lymphatic vessel function; Lymphoedema