3. DiscussionThe lymphatic system is specialized in the uptake of lymph from the interstitial space, absorption of dietary lipids from the small intestine, and immune surveillance [64]. Because lymphatic markers were identified much later than blood vessel markers, research on the lymphatic system is quite new compared to that on the blood vasculature. The importance of lymphatic vessels in health and disease is not yet well established. To this end, the work of this thesis aimed to identify molecules specifically expressed in lymphatic vessels. When analyzing transcriptomic data comparing blood and lymphatic endothelial cells, it was determined that CD36 was specifically upregulated in LECs of HDMECs in the tube formation assay. Therefore, research has been directed towards uncovering the role of CD36 in the lymphatic system in vitro and in vivo. In vitro assays showed that CD36 was required for LEC migration and proliferation. Furthermore, the effects of this soluble receptor were also structurally and functionally analyzed in detail in the skin of CD36 null mice and WT littermates. The in vivo experiments focused on the skin since the cellular experiments focused on dermal LECs. The function of dermal lymphatics was analyzed in three different assays. In skin absorption experiments, Evans blue and FITC dextran were injected intradermally and lymphatic absorption was visualized. Since these absorption experiments were qualitative, a quantitative test was sought to measure lymphatic function. In a report on Emilin-deficient mice, Evans blue was injected into the footpad and lymph nodes were quantitatively analyzed if they had the same dye content (167). However, this test had a limited window on q...... middle of article ...... mice treated with anti-VEGFR3 because the lymphatics in the aortic wall were disrupted, highlighting the importance of the vessels lymphatics in RCTs. [191].In conclusion, this work highlights important biological aspects of lymphangiogenesis. It also highlights the role of aging on lymphatic function, determined by a new lymphatic uptake test. Furthermore, data from the present thesis show the previously undetermined role of CD36 in adipocyte and lymphatic biology, with emphasis on aging assessed by a unique Western dietary protocol. Although the results of a high-fat diet imply that loss of CD36 may ameliorate obesity, this work suggests that such treatment should be carefully considered before implementation. Furthermore, studies involving conditional loss of CD36 in adipocytes of different ages would allow us to specifically determine the effects of CD36 loss on metabolism and aging...