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- Title
HIV Protease Inhibitors Impair Palmitate Oxidation in L6 Myotubes and 3T3-L1 Adipocytes.
- Authors
Carper, Michael J.; Yarasheski, Kevin E.; Hruz, Paul W.; Ramanadham, Sasanka
- Abstract
Inclusion of protease inhibitors to current highly active antiretroviral therapy [HAART] for patients with HIV-1 has dramatically improved morbidity and mortality among this population by increasing CD4 counts, and suppressing HIV viral load and opportunistic infections. However, the occurrence of metabolic abnormalities, such as insulin resistance, diabetes mellitus, dyslipidemia, central adiposity, and peripheral lipodystrophy are dramatically increasing. The purpose of this investigation was to determine the effects of HIV protease inhibitors, currently used in the treatment of the HIV[sup +] population, on [sup 14]C-palmitate oxidation (FAO) in L6 myotubes and 3T3-L1 adipocytes. Differentiated L6 myoblasts were exposed to 1µM, 10µM, or 20µM (n=6 per treatment) indinavir (IDV), ritonavir (RTV), ritonavir/atazanavir (RTV/ATV), and ritonavir/lopinavir (RTV/LPV) for 3h. Differentiated 3T3-L1 adipocytes were exposed to 1µM, 10µM, and 20µM (n=6 per treatment) IDV and RTV for 3h. [sup 14]C-labeled carbon dioxide production was analyzed by liquid scintillation to determine FAO in both culture systems. Results are expressed as percent (%) decrease in [sup 14]C-labeled CO[sub 2] production. In L6 myotubes: IDV significantly decreased FAO at 1 µM (27.4%), 10µM (23.8%), and 20µM (26.2%); RTV significantly decreased FAO at 20µM (44%); RTV/ATV significantly decreased FAO at 10µM (54%) and 20µM (57%); and RTV/LPV significantly decreased FAO at 10µM (52%) and 20µM (61%). In 3T3-L1 adipocytes: IDV significantly decreased FAO at 1µM (45%), 10µM (50%), and 20µM (50%); and RTV significantly decreased FAO at 20µM (45%). In conclusion, this is the first investigation to report the effects of protease inhibitors on skeletal muscle and adipose tissue fatty acid oxidation. Treatment of these tissues with IDV, RTV, RTV/ATV, and RTV/LPV significantly decreased FAO and provides important new evidence that protease inhibitors have direct affects on fatty acid metabolism. Decreased FAO might be speculated to increase the availability of circulating free fatty acids which would contribute to the development of peripheral insulin resistance and hyperglycemia.
- Subjects
HIV virus enzymes; PROTEASE inhibitors; PALMITIC acid; FAT cells; FATTY acids; OXIDATION
- Publication
Diabetes, 2007, Vol 56, pA368
- ISSN
0012-1797
- Publication type
Article