Obesity-Associated Conditions Hinder Solute Drainage Function of Engineered Human Lymphatic Vessels

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Obesity Research

Background:

• Obesity is linked to impaired lymphatic solute drainage.
• The direct impact of obesity-associated chronic inflammation, hypoxia, and hyperlipidemia on lymphatic function remains unclear.
• It is unknown if these effects are mediated directly by lymphatic endothelial cells (LECs) or indirectly by the tissue microenvironment.

Purpose of the Study:

• To investigate whether obesity-associated inflammation, hypoxia, and hyperlipidemia impair lymphatic solute drainage.
• To determine if these impairments act directly on LECs or are mediated by the tissue microenvironment.

Main Methods:

• Engineered blind-ended lymphatic vessels in collagen gels.
• Simulated obesity using TNF-α, CoCl2, and oleate to model inflammation, hypoxia, and hyperlipidemia.
• Assessed solute drainage and leakage in simulated obese microenvironments, stiffened gels, adipocyte-laden gels, and with conditioned media from treated adipose cells.

Main Results:

• Simulated obesity directly impaired lymphatic solute drainage and increased leakage by affecting endothelial junctions.
• These effects occurred regardless of matrix stiffness.
• Conditioned media from treated adipose cells and lymphatics in adipocyte-laden gels did not worsen lymphatic function.

Conclusions:

• Obesity-associated inflammation, hypoxia, and hyperlipidemia directly impair LECs, leading to reduced lymphatic solute drainage.
• Adipocytes may have a protective role against obesity-induced lymphatic dysfunction.