NDLI: Long-Term Treatment with Lopinavir-Ritonavir Induces a Reduction in Peripheral Adipose Depots in Mice▿

Content Provider	PubMed Central
Author	Prot, Matthieu Laurence, Heripret Cardot-leccia, Nathalie Perrin, Christophe Aouadi, Myriam Thibaud, Lavrut Garraffo, Rodolphe Dellamonica, Pierre Durant, Jacques Le, Marchand-brustel Yannick Bernard, Binétruy
Copyright Year	2006
Abstract	Highly active antiretroviral therapy (HAART) of human immunodeficiency virus-infected patients is associated with adverse effects, such as lipodystrophy and hyperlipidemia. The lipodystrophic syndrome is characterized by a peripheral lipoatrophy and/or fat accumulation in the abdomen and neck. In order to get insights into the physiopathological mechanisms underlying this syndrome, we treated mice with protease inhibitors (PIs) over a long period of time. Although atazanavir-treated mice presented the same circulating triglyceride concentration as control mice, lopinavir-ritonavir-treated mice rapidly became hypertriglyceridemic, with triglyceride levels of 200 mg/dl, whereas control and atazanavir-treated animals had triglyceride levels of 80 mg/dl. These results obtained with mice reproduce the metabolic disorder observed in humans. White adipose tissue (WAT) was analyzed after 8 weeks of treatment. Compared to the control or atazanavir treatment, lopinavir-ritonavir treatment induced a significant 25% weight reduction in the peripheral inguinal WAT depot. By contrast, the profound epididymal WAT depot was not affected. This effect was associated with a 5.5-fold increase in SREBP-1c gene expression only in the inguinal depot. Our results demonstrate that the long-term treatment of mice with PIs constitutes an interesting experimental model with which some aspects of the lipoatrophy induced by HAART in humans may be studied.
Related Links	http://dx.doi.org/10.1128/aac.00625-06
Ending Page	4004
Page Count	7
Starting Page	3998
File Format	PDF
ISSN	00664804
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	12
Volume Number	50
Language	English
Publisher	American Society for Microbiology
Publisher Date	2006-12-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Pharmacology (medical) Pharmacology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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