Leptin is a
hormone produced by adipose tissue that regulates various physiological processes. Recent studies have shown that the level of circulating
leptin is elevated in obese patients and have suggested a relationship between
obesity and postoperative
lymphedema. However, the mechanisms by which postoperative
lymphedema develops in obese patients and the mechanisms by which
leptin regulates lymphatic endothelial cell homeostasis such as tube formation and cell proliferation remain unknown. Here we report that
leptin regulates tube formation and cell proliferation in human dermal lymphatic endothelial cells (HDLECs) by activation of the
signal transducer and activator of transcription 3 pathway, which is downstream signaling of the
leptin receptor. Additionally, we found that upregulation of suppressor of
cytokine signaling 3 underlies the mechanisms by which a high dose of
leptin inhibits cell proliferation and tube formation.
Leptin also enhanced expression of the proinflammatory
cytokine IL-6 in HDLECs. Interestingly,
IL-6 rescues the compromised cell proliferation and tube formation caused by treatment with a high dose of
leptin in an autocrine or paracrine manner. Taken together, our findings reveal a novel mechanism by which compromised HDLECs maintain their homeostasis during
inflammation mediated by
leptin and
IL-6. Thus, regulating the level of
leptin or
IL-6 may be a viable strategy to reduce the incidence of postoperative
lymphedema.