Inducible lymphatic hyperplasia to drive chylous accumulation mimicking lymphangiomatosis

PI: Joseph Rutkowski, PhD

Institution: Texas A&M Health Science Center

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One common complication of GLA and Gorham-Stout Disease is chylothorax, the leaking of chylous lymph – lymph transporting dietary fatty acids from the gut – into the thoracic space resulting in difficulty breathing and local inflammation. The mechanisms of chylothorax are unknown, but we have developed a mouse model overexpressing VEGF-D, a lymphangiogenic growth factor – in adipocytes that, surprisingly, exhibited chylothorax when combined with chronic high fat diet feeding. We sought to identify how different dietary fatty acids (unsaturated v. saturated) impacted the propensity for chylothorax formation and whether inflammation markers or changes in body composition could predict this.

Adipose VEGF-D mice were protected from the metabolic syndrome (insulin resistance, hyperlipidemia, etc.) with reduced inflammation when placed on chronic high fat diet. Despite this, chylothorax still developed, with, surprisingly, saturated fat diet presenting the lowest incidence. This, despite the palm oil diet causing the most inflammation. Our findings suggest that overall lymphatic integrity, rather than diet per se, drives chylothorax in this model. We continue to work in identifying these mechanisms.