Mesenteric lymphatic dysfunction promotes insulin resistance and represents a potential treatment target in obesity

Abstract

Visceral adipose tissue (VAT) encases mesenteric lymphatic vessels and lymph nodes through which lymph is transported from the intestine and mesentery. Whether mesenteric lymphatics contribute to adipose tissue inflammation and metabolism and insulin resistance is unclear. Here we show that obesity is associated with profound and progressive dysfunction of the mesenteric lymphatic system in mice and humans. We find that lymph from mice and humans consuming a high-fat diet (HFD) stimulates lymphatic vessel growth, leading to the formation of highly branched mesenteric lymphatic vessels that ‘leak’ HFD-lymph into VAT and, thereby, promote insulin resistance. Mesenteric lymphatic dysfunction is..