Dysfunctional adipose tissue-lymphatic crosstalk in obesity

The lymphatic vasculature is recognized for its roles in immunity, lipid transport and fluid homeostasis, but has been ignored, until recently, for its involvement in adipose tissue metabolism, obesity and associated comorbidities. States of overnutrition, such as in obesity, are associated with impairment of lymphatic function, leading to localized lymphoedema, adipogenesis and insulin resistance. Conversely, compromised lymphatic vasculature integrity can induce adiposity and accelerate insulin resistance. Through the use of advanced 'omics' and bioinformatic technologies coupled with functional experiments in cells, mice and humans, we now know that the lymphatic system is more than just a transport conduit and is intimately involved in tissue and organ homeostasis, including in adipose tissue. In this Review, we summarize the interconnected causes of obesity and lymphatic dysfunction with a particular focus on delineating the underappreciated yet fundamental crosstalk between the lymphatic network and white and brown adipose tissues. We also synthesize information on lymph-directed therapeutic strategies that have the potential to transform outcomes in obesity.