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Horm Metab Res 2005; 37(10): 602-609
DOI: 10.1055/s-2005-870526
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

The Effect of the HIV Protease Inhibitor Ritonavir on Proliferation, Differentiation, Lipogenesis, Gene Expression and Apoptosis of Human Preadipocytes and Adipocytes

S.  Grigem1 , P.  Fischer-Posovszky1 , K. M.  Debatin1 , E.  Loizon2 , H.  Vidal2 , M.  Wabitsch1
  • 1Department of Pediatrics, University of Ulm, Germany
  • 2UMR INSERM U449/INRA U1235, Faculté de médecine RTH Laennec, Lyon, France
Further Information

Publication History

Received 19 January 2005

Accepted after revision 25 April 2005

Publication Date:
08 November 2005 (online)

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Abstract

HIV patients in highly active antiretroviral therapy (HAART) develop lipodystrophy and insulin resistance. Protease inhibitors have been shown to alter adipocyte metabolism in murine cell lines. In this study, biological effects of the HIV protease inhibitor, ritonavir, were investigated on human SGBS preadipocytes and adipocytes. Ritonavir dose-dependently impaired preadipocyte proliferation and adipogenic differentiation. Gene expression analysis measured by real-time PCR, showed no effect of ritonavir (up to 20 μM) on expression of mRNA of PPARγ2 and SREBP1c, but suppressed adiponectin mRNA while increasing IL-6 mRNA expression. In human adipocytes, ritonavir at therapeutic concentrations inhibited insulin-stimulated lipogenesis, reduced GLUT4 mRNA, fatty acid synthase and adiponectin expression, while increasing IL-6 mRNA expression. Finally, long-term treatment (72 and 120 h) of SGBS adipocytes but not preadipocytes with ritonavir induced apoptosis in up to 15 % of the cells. All together, these data show effects of ritonavir on human preadipocytes and adipocytes aiming at reducing adipose tissue mass and increasing insulin resistance. These in vitro findings may partly explain the clinical findings in patients under HAART. Furthermore, SGBS cells may serve as a useful tool in further investigation of the mechanism of protease inhibitor action in human adipocytes.

Key words

Lipodystrophy - HAART - Fat cell - SGBS-cells - Insulin resistance

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Martin Wabitsch, M. D.

Pediatric Endocrinology and Diabetology, Department of Pediatrics and Adolescent Medicine

University of Ulm · Prittwitzstraße 43 · 89075 Ulm · Germany

Phone: +49 (731) 500-277 15 ·

Fax: +49 (731) 500-267 14

Email: martin.wabitsch@medizin.uni-ulm.de

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