Objective: Significant advances in the treatment of the morbidity and mortality associated with AIDS are also associated with undesirable side-effects in fat redistribution (lipodystrophy), insulin resistance and cardiovascular risk, which is directly linked to protease inhibitor (PI) treatment.
Methods: The effects of four different PIs on triglyceride (TG) storage and adipokine production (leptin, adiponectin, and acylation stimulating protein [ASP]) in omental (OM) and subcutaneous (SC) adipose tissues were examined.
Results: Initial results demonstrated that saquinivir (SQV) and ritonivir (RTV) had little observed effect on de novo TG synthesis ([3H]glucose incorporation into TG) or fatty acid re-esterification ([14C]oleate incorporation into TG), whereas amprenivir (APV) and indinivir (IDV) reduced TG synthesis, especially in SC tissue up to 30+/-5.8% P<0.05 and 46+/-7.8% P<0.001, at 20 microM, respectively. There was no observed effect on phospholipid synthesis, tissue protein or toxicity. Only APV and IDV decreased leptin and adiponectin secretion in SC tissue, in a time- and concentration-dependent manner: at 18 h, leptin was inhibited by 54+/-3.1% (P<0.001) and 44+/-6.4% (P<0.001) by APV and IDV (40 microM), respectively, and adiponectin was inhibited by 35+/-5.6%(P<0.001) and 25+/-12.3% (P<0.05) by APV and IDV (40 IuM), respectively. By contrast, both IDV and APV decreased ASP secretion in OM tissues by a maximum of 53 +/-7.8% (P<0.001) and 59+/-5.9% (P<0.001), respectively, and by a maximum of 86+/-1.6% (P<0.001) and 72 +/-4% (P<0.001), respectively, in SC tissues.
Conclusion: PI have a direct effect on human adipose tissue which are site, PI and adipokine specific; these effects may contribute to the overall adipose imbalance and development of lipodystrophy, and metabolic syndrome in HIV-positive individuals.