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Obesity but not high-fat diet impairs lymphatic function.

G D García Nores1, D A Cuzzone1, N J Albano1

  • 1Division of Plastic and Reconstructive Surgery, The Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

International Journal of Obesity (2005)
|May 21, 2016
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Summary

High-fat diets impair lymphatic function, especially in obesity-prone individuals. This occurs due to inflammation and altered gene expression in lymphatic endothelial cells (LECs), suggesting VEGFR-3 signaling as a therapeutic target.

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Area of Science:

  • Lymphatic biology
  • Obesity research
  • Cellular signaling

Background:

  • High-fat diet (HFD)-induced obesity negatively impacts lymphatic function.
  • The direct role of HFD versus adipose tissue deposition in lymphatic dysfunction is unclear.

Purpose of the Study:

  • To investigate the effects of HFD on lymphatic function in obesity-prone and obesity-resistant mice.
  • To elucidate the cellular and molecular mechanisms underlying HFD-induced lymphatic impairment.

Main Methods:

  • Comparative analysis of lymphatic function in vivo and in vitro between obesity-prone and obesity-resistant mice fed HFD.
  • Assessment of lymphatic endothelial cell (LEC) gene expression (VEGFR-3, Prox1) and apoptosis.
  • In vitro experiments exposing LECs to fatty acids and manipulating VEGFR-3 signaling.

Main Results:

  • Obesity-prone mice exhibited impaired lymphatic function, increased perilymphatic inflammation, and lipid droplet accumulation around LECs.
  • LECs from obesity-prone mice showed reduced VEGFR-3 and Prox1 expression compared to obesity-resistant mice.
  • In vitro, fatty acid exposure induced LEC apoptosis and decreased VEGFR-3, while inhibiting VEGFR-3 pathway inhibitors improved viability.

Conclusions:

  • HFD-induced obesity impairs lymphatic function via increased perilymphatic inflammation and altered LEC gene expression.
  • Diminished VEGFR-3 signaling in LECs contributes to lymphatic dysfunction.
  • Restoring VEGFR-3 signaling may offer a therapeutic strategy to improve lymphatic function in obesity.