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AIDS Research and Therapy

, 4:8

First Online: 01 May 2007Received: 21 November 2006Accepted: 01 May 2007


Protease inhibitors, as part of highly active anti-retroviral therapy HAART, have significantly increased the lifespan of human immunodeficiency virus HIV infected patients. Several deleterious side effects including dyslipidemia and lipodystrophy, however, have been observed with HAART. Women are at a higher risk of developing adipose tissue alterations and these alterations have different characteristics as compared to men. We have previously demonstrated that in mice the HIV protease inhibitor, ritonavir, caused a reduction in weight gain in females, but had no effect on male mice. In the present study, we examined the potential causes of this difference in weight gain. Low-density lipoprotein receptor LDL-R null mice or wild-type C57BL-6 mice, were administered 15 μg-ml ritonavir or vehicle 0.01% ethanol in the drinking water for 6 weeks. The percent of total body weight gained during the treatment period was measured and confirmed that female LDL-R gained significantly less weight with ritonavir treatment than males. In wild type mice, however, there was no effect of ritonavir treatment in either sex. Despite the weight loss in LDL-R null mice, ritonavir increased food intake, but no difference was observed in gonadal fat weight. Serum leptin levels were significantly lower in females. Ritonavir further suppressed leptin levels in p < 0.05. Ritonavir did not alter serum adiponectin levels in either gender. To determine the source of these differences, female mice were ovariectomized remove the gonadal sex hormones. Ovariectomy prevented the weight loss induced by ritonavir p < 0.05. Furthermore, leptin levels were no longer suppressed by ritonavir p < 0.05. This study demonstrates that gonadal factors in females influence the hormonal control of weight gain changes induced by HIV protease inhibitors in an environment of elevated cholesterol.

Electronic supplementary materialThe online version of this article doi:10.1186-1742-6405-4-8 contains supplementary material, which is available to authorized users.

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Autor: Melinda E Wilson - Kimberly F Allred - Elizabeth M Kordik - Deana K Jasper - Amanda N Rosewell - Anthony J Bisotti


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