Lipid Biology and Lymphatic Function: A Dynamic Interplay with Important Physiological and Pathological Consequences

Lymphatic vessels have been traditionally considered as passive transporters of lipids particularly from the intestine. However, it became apparent from emerging research that lymphatic vessel can play a more extensive role in lipid metabolism than previously realized. Moreover, recent evidence reveal that lipid deposition in the form of white adipose tissue or cholesterol as observed in obesity or hypercholesterolemia, respectively, may perturb lymphatic function. This Review summarizes the evidence supporting a bidirectional relationship between lymphatic function and the deposition of white adipose or cholesterol in peripheral tissue in the context of obesity and hypercholesterolemia. We also discuss potential mechanisms whereby excessive fat or cholesterol accumulation in tissue may account for lymphatic dysfunction. We particularly consider how phenotypic and functional changes in adipose tissue as well as in macrophages accompanying obesity and hypercholesterolemia may affect the lymphatic vasculature. In addition to their transport function, lymphatic vessels play essential roles in regulating inflammatory and adaptive immune responses. Therefore, we highlight how lymphatic dysfunction associated with hypercholesterolemia may influence immunity, inflammation and the significance to atherosclerosis. The emerging importance of the lymphatic system in lipid metabolism and immunity underscores the urgent need to find pharmacological or surgical interventions that can improve lymphatic function which are currently not available.