Leptin, the Product of Ob Gene, Promotes Angiogenesis

TLDR

Leptin, an adipocyte‑derived cytokine, regulates satiety and energy expenditure and is hypothesized to influence angiogenesis, impacting obesity and tissue growth. The study aimed to test whether leptin modulates vascular growth during fat mass development. The authors examined leptin receptor expression in human and porcine endothelial cells using Western blot and RT‑PCR, and then tested leptin effects on cultured HUVECs. Leptin activated Erk1/2 phosphorylation, stimulated endothelial proliferation and tube formation in vitro, and promoted neovascularization in vivo, demonstrating that leptin via Ob‑R activates a tyrosine‑kinase pathway to drive angiogenesis.

Abstract

Abstract —The adipocyte-derived cytokine leptin is thought to play a key role in the control of satiety and energy expenditure. Because adipogenesis and angiogenesis are tightly correlated during the fat mass development, we tested the hypothesis that leptin is able to modulate the growth of the vasculature. Experiments were performed using cultured human umbilical venous endothelial cells (HUVECs) and porcine aortic endothelial cells. The presence of 170-kDa endothelial leptin receptor (Ob-R) was assessed in HUVECs by Western blot analysis. Reverse transcriptase–polymerase chain reaction analysis using specific oligonucleotides for the short and long Ob-R forms further revealed the expression of both Ob-R transcripts in endothelial cells. Moreover, leptin evoked a time-dependent tyrosine phosphorylation of a number of endothelial proteins, the most prominent of which were the mitogen-activated protein kinases Erk1/2. Treatment of HUVECs with leptin led to a concentration-dependent increase in cell number that was maximal at 10 ng/mL leptin and equivalent to that elicited by vascular endothelial growth factor. This effect was associated with an enhanced formation of capillary-like tubes in an in vitro angiogenesis assay and neovascularization in an in vivo model of angiogenesis. These results indicate that leptin, via activation of the endothelial Ob-R, generates a growth signal involving a tyrosine kinase-dependent intracellular pathway and promotes angiogenic processes. We speculate that this leptin-mediated stimulation of angiogenesis might represent not only a key event in the settlement of obesity but also may contribute to the modulation of growth under physiological and pathophysiological conditions in other tissues.