PMID- 17310812
OWN - NLM
STAT- MEDLINE
DCOM- 20070315
LR  - 20181201
IS  - 1359-6535 (Print)
IS  - 1359-6535 (Linking)
VI  - 11
IP  - 6
DP  - 2006
TI  - Protease inhibitor effects on triglyceride synthesis and adipokine secretion in 
      human omental and subcutaneous adipose tissue.
PG  - 681-91
AB  - 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.
FAU - Cianflone, Katherine
AU  - Cianflone K
AD  - Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health 
      Centre, Montreal, Quebec, Canada. katherine.cianflone@crhl.ulaval.ca
FAU - Zakarian, Robert
AU  - Zakarian R
FAU - Stanculescu, Cristina
AU  - Stanculescu C
FAU - Germinario, Ralph
AU  - Germinario R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Adiponectin)
RN  - 0 (HIV Protease Inhibitors)
RN  - 0 (Leptin)
RN  - 0 (Triglycerides)
SB  - IM
MH  - Adiponectin/*metabolism
MH  - Adipose Tissue/drug effects/metabolism
MH  - Adult
MH  - Female
MH  - HIV Protease Inhibitors/*pharmacology
MH  - HIV-Associated Lipodystrophy Syndrome/physiopathology
MH  - Humans
MH  - Leptin/*metabolism
MH  - Lipid Metabolism
MH  - Male
MH  - Middle Aged
MH  - Omentum/*metabolism
MH  - Subcutaneous Fat/drug effects/*metabolism
MH  - Triglycerides/*metabolism
EDAT- 2007/02/22 09:00
MHDA- 2007/03/16 09:00
CRDT- 2007/02/22 09:00
PHST- 2007/02/22 09:00 [pubmed]
PHST- 2007/03/16 09:00 [medline]
PHST- 2007/02/22 09:00 [entrez]
PST - ppublish
SO  - Antivir Ther. 2006;11(6):681-91.