Leptin induces angiopoietin-2 expression in adipose tissues

Adipose tissues consisting of adipocytes, microvasculature, and stroma are completely ablated upon overexpression of leptin in rats. This tissue regre ssion is mediated by enhanced lipid beta-oxidation, adipocyte dedifferentia tion, and apoptosis. To further characterize this phenomenon, we studied th e possible effect of leptin on the adipose microvasculature. Tissue microva sculature is maintained by the interplay between positive and negative sign als mediated by factors including vascular endothelial growth factor (VEGF) , basic fibroblast growth factor, angiopoletin-1 (Ang-1), and Ang-2. Expres sion of the negative signal Ang-2 was reported in fetal tissues and in the adult ovary, which undergoes vascular remodeling or regression. We demonstr ate that leptin induces the expression of Ang-a in adipose tissue without a concomitant increase in VEGF. Induction of Ang-2 occurred in an autocrine manner, as demonstrated in cultured adipocytes but not in several other cel l types. This tissue-specific induction of Ang-2 coincided with initiation of apoptosis in adipose endothelial cells. We propose that induction of Ang -2 by leptin in adipose cells is one of the events leading to adipose tissu e regression.