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Papers In Press, published online ahead of print January 4, 2001
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100
Corresponding Author: menachem.rubinstein{at}weizmann.ac.il
Adipose tissues consisting of adipocytes, microvasculature and stroma are completely ablated upon over-expression of leptin in rats. This tissue regression is mediated by enhanced lipid beta-oxidation, adipocyte de-differentiation and apoptosis. To further characterize this phenomenon, we studied the possible effect of leptin on the adipose microvasculature. Tissue microvasculature is maintained by the interplay between positive and negative signals mediated by factors including VEGF, bFGF, Angiopoietin-1 (Ang-1) and Ang-2. Expression of the negative signal Ang-2 was reported in fetal tissues and in the adult ovary, which undergoes vascular remodeling or regression. We demonstrate that leptin induces the expression of Ang-2 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 cell 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 tissue regression.
J. Biol. Chem, 10.1074/jbc.C000634200
Submitted on September 12, 2000
Revised on December 13, 2000
Accepted on January 4, 2001
Leptin induces angiopoietin-2 expression in adipose tissues
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