The HIV protease inhibitor saquinavir impairs lipid metabolism and glucose transport in cultured adipocytes

in Journal of Endocrinology
Authors:
S Ranganathan
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PA Kern
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DOI:
https://doi.org/10.1677/joe.0.1720155
Volume/Issue:
Volume 172: Issue 1
Article Type:
Other
Page Range:
155–162
Online Publication Date:
01 Jan 2002
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Treatment of HIV infection using protease inhibitors is frequently associated with lipodystrophy and impaired lipid and glucose metabolism. We examined the effect of saquinavir, one of the protease inhibitors, on lipid metabolism and glucose transport in cultured adipocytes. Saquinavir inhibited lipoprotein lipase (LPL) activity in 3T3-F442A and 3T3-L1 adipocytes. The inhibition of LPL was 81% at a concentration of 20 microg/ml. Another closely related drug, indinavir, had a small inhibitory effect. Saquinavir also inhibited the biosynthesis of lipids from [(14)C]-acetate. Saquinavir increased the lipolysis. Saquinavir had no significant effect on the cellular protein synthesis or protein content. Saquinavir increased the basal glucose transport threefold and decreased insulin-stimulated glucose transport by 35%. These studies suggest that some HIV protease inhibitors have direct effects on lipid and glucose metabolism. This inhibition of lipogenesis and glucose transport may explain some of the lipodystrophy, dyslipidemia and disturbed glucose metabolism with the clinical use of these drugs.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Page(s):
8
Article Type:
Other
Print Publication Date:
01 Jan 2002
Online Publication Date:
01 Jan 2002