Figure 2: Possible mechanisms contributing to impaired lymphatic function during obesity and/or hypercholesterolemia. In skin, dermal blind-ended initial lymphatic vessels converge into collecting vessels, which are covered with smooth muscles and feed into the draining lymph node (not represented here). Under healthy condition, macrophages present in both the dermis and subcutaneous fat and adipocytes may maintain the morphology and the function of lymphatic vessels by secreting vascular endothelial growth factor-C (VEGF-C) and adiponectin as well as controlling the expression of eNOS. In contrast, obesity and hypercholesterolemia have been shown to induce infiltration of macrophages which transform into foam cells upon cholesterol uptake and adipocyte hypertrophy and death. Under these conditions, adipocytes produce reduced amount of adiponectin but increased reactive oxygen species (ROS) which have been shown to reduce lymphatic pumping activity. Lipid-laden macrophages may show reduced capacity to produce VEGF-C. Furthermore, obesity is associated with increased deposition of extracellular matrix (ECM), particularly collagen which may in turn affect lymphatic vasculature. Altogether, these alterations in macrophage and adipocyte along with fibrosis may lead to lymphatic vessel dilation and impaired lymphatic transport.