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Angiotensin II Receptors in Human Preadipocytes: Role in Cell Cycle Regulation

Wyeth-Ayerst Research, Princeton, New Jersey 08543; and the Department of Surgery, State University of New York Health Science Center (J.G.K.), Brooklyn, New York 11203

Address all correspondence and requests for reprints to: Dr. David L. Crandall, Wyeth-Ayerst Research, CN 8000, Princeton, New Jersey 08543. E-mail: crandad{at}war.wyeth.com

The role of angiotensin II (AII) in human preadipocyte physiology has been investigated in primary cultures from human adipose tissue. Receptor binding studies indicated that human preadipocytes express a high affinity AII binding site of the AT₁ subtype, as binding of ¹²⁵I-labeled [Sar¹,Ile⁸]AII was rapid, saturable, and specific. As AII has previously been demonstrated to affect the cell cycle in adrenal and cardiac cells, the effect of AII on regulation of cycle progression was examined in human preadipocytes. Stimulation of preadipocytes with AII resulted in G₁ phase progression of the cell cycle, as determined by flow cytometric analysis. AII treatment was associated with induction of expression of the messenger RNA for the cell cycle regulatory protein cyclin D1 in a dose-dependent manner. Pretreatment of cells with subtype-selective AT receptor ligands before AII stimulation indicated that the cyclin response was mediated via the AT₁ receptor. The identity of the cells as preadipocyte was verified by culture in a defined differentiation medium, observing both leptin message expression and triglyceride accumulation by flow cytometry. These findings indicate that AII has early, receptor-mediated effects on cell cycle progression in human preadipocytes that may contribute to differentiation to the adipocyte phenotype.

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