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Originally published In Press as doi:10.1074/jbc.C000634200 on January 4, 2001

J. Biol. Chem., Vol. 276, Issue 11, 7697-7700, March 16, 2001
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ACCELERATED PUBLICATION
Leptin Induces Angiopoietin-2 Expression in Adipose Tissues*

Batya CohenDagger §, Dalit BarkanDagger §, Yinon LevyDagger , Iris Goldberg, Eduard Fridman, Juri Kopolovic, and Menachem RubinsteinDagger ||

From the Dagger  Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel and the  Department of Pathology, Sheba Medical Center, Ramat Gan 52621, Israel

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 dedifferentiation, 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 vascular endothelial growth factor (VEGF), basic fibroblast growth factor, 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.

* This work was supported by the Ares Serono Group of Companies.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ These authors contributed equally to the study.

|| Incumbent of the Edna and Maurice Weiss Chair of cytokine research. To whom correspondence should be addressed. E-mail: menachem.rubinstein@weizmann.ac.il.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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