Supplementary Material for: High-Fat Diet in the Absence of Obesity Does Not Aggravate Surgically Induced Lymphoedema in Mice

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.