Protease inhibitor effects on triglyceride synthesis and adipokine secretion in human omental and subcutaneous adipose tissue.
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.


CONCLUSIONS
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.
Cianflone
Katherine
K
Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre, Montreal, Quebec, Canada. katherine.cianflone@crhl.ulaval.ca
Zakarian
Robert
R
Stanculescu
Cristina
C
Germinario
Ralph
R
D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D005260:Female; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000503:physiopathology; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D009852:Omentum / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D052242:Adiponectin; D017320:HIV Protease Inhibitors; D020738:Leptin; D014280:Triglycerides