Characterization of Lymphangiogenesis in Adipose Tissue Upon Local, Induced VEGF‐D Overexpression

Abstract

Inflammatory adipose tissue expansion is the root of the metabolic syndrome in obesity. Insulin‐resistant adipocytes and dysregulated lipolysis results in increased circulating lipids, ectopic lipid deposition, and systemic insulin resistance. Lymphangiogenesis ‐ expansion of the lymphatic vessel network ‐ is a necessary process in clearing fluid and immune cells during inflammation. Lymphatic capillaries are, however, largely absent from murine adipose tissues making induced lymphangiogenesis a potential target in adipose inflammation. We have previously described a mouse model of inducible, adipose tissue‐specific expression of murine VEGF‐D that exhibits de novo lymphangiogenesis in white and brown adipose tissue. Our previous studies suggest that enhanced adipose lymphangiogenesis reduces obesity‐associated inflammation and improves adipose metabolism. We have observed that induced adipose lymphangiogenesis is only robust after nearly 4 months of elevated VEGF‐D levels and the extent varies across adipose depots in Adipo‐VD mice. The mechanism of VEGF‐D initiated lymphatic formation in each adipose depot is therefore potentially different, with processes involving either sprouting or lymphvasculogenesis. Our current work quantifies the lymphangiogenic time‐course, studying adipose tissues at 1, 2, 3, and 4, months following VEGF‐D induction. Comparison across adipose depots, sex, and diet (chow versus 60% kcal from fat diet) are made using qPCR for lymphatic markers as well as immunofluorescence of lymphatic structures on fixed and whole mount tissues. Correlation of adipose tissue macrophage infiltration/accumulation with lymphatic density are also performed. In addition to a quantified time course, our whole mount imaging and lineage tracing suggest that lymphangiogenesis in subcutaneous adipose depots – the white inguinal and brown interscapular – may arise from dermal lymphatic endothelium. Understanding how lymphatics grow and impact adipose tissue health thus provides a novel target in obesity's metabolic syndrome.Support or Funding InformationLIPEDEMA FOUNDATIONThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.