Defective lymphatic vasculature in obesity.

Lymphedema is an important, and often underdiagnosed complication of obesity and is likely due to acquired defects in the lymphatic vasculature. Study of diet-induced obesity animal models have indicated defective lymphatic vasculatures might extend to other anatomical sites, especially visceral depots. Excess mechanical pressure, metabolites, pro-inflammatory cytokines, and adipokines released during adipose tissue expansion can predispose lymphocytes to overactivation and apoptosis; compromising collecting lymphatic vessels; and triggering lymph node hypoplasia, fibrosis, and apoptosis. Consequently, the defective lymphatic vasculature may disrupt local and systemic immune-metabolic homeostasis, contributing to various adverse outcomes including inflammation and immune dysfunction, abnormal transport dynamics of lipids, vitamin D, and possibly incretin in obesity. Weight reduction is the definitive management to restore lymphatic function and should be instituted before permanent vasculature impairment develops. Besides lymphatic regeneration, future research aimed at elucidating the pathophysiological mechanisms between adipose tissue and lymphatic vasculature should be considered to help the development of potential adjunctive therapies that might repair the lymphatic vasculature, improve immune-metabolic outcomes, and even combat obesity.