Obesity but not high-fat diet impairs lymphatic function.

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.