Adiponectin Ameliorates Dyslipidemia Induced by the Human Immunodeficiency Virus Protease Inhibitor Ritonavir in Mice
| Autor: | Aimin Xu, Kok Weng Chan, Lai-Ching Wong, Shinan Yin, Karen S.L. Lam |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Hormone Replacement Therapy Blotting Western Gene Expression Hyperlipidemias Fatty Acids Nonesterified Biology Mice chemistry.chemical_compound Endocrinology immune system diseases Indinavir Internal medicine Hyperlipidemia Adipocytes medicine Animals Protease inhibitor (pharmacology) Triglycerides chemistry.chemical_classification Ritonavir Dose-Response Relationship Drug Triglyceride Adiponectin Fatty Acids Proteins virus diseases Fatty acid 3T3 Cells HIV Protease Inhibitors biochemical phenomena metabolism and nutrition Blotting Northern medicine.disease Recombinant Proteins Mice Inbred C57BL Cholesterol Nelfinavir Liver chemistry Intercellular Signaling Peptides and Proteins Oxidation-Reduction medicine.drug |
| Zdroj: | Endocrinology. 145:487-494 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2003-1140 |
| Popis: | Although the clinical application of HIV protease inhibitors (PIs) has markedly reduced HIV-related morbidity and mortality, it is now recognized that PI-based therapy often causes serious metabolic disorders, including hyperlipidemia and premature atherosclerosis. The etiology of these adverse effects remains obscure. Here, we demonstrate that deficiency of the fat-derived hormone adiponectin might play a role. The steady-state mRNA levels of the adiponectin gene and secretion of this protein from 3T3-L1 adipocytes are significantly decreased after treatment with several PIs (indinavir, nelfinavir, and ritonavir), with ritonavir having the greatest effect. Intragastric administration of ritonavir into mice decreases plasma concentrations of adiponectin and concurrently increases the plasma levels of triglyceride, free fatty acids, and cholesterol. Adiponectin replacement therapy markedly ameliorates ritonavir-induced elevations of triglyceride and free fatty acids. These beneficial effects of adiponectin are partly due to its ability to decrease ritonavir-induced synthesis of fatty acids and triglyceride, and to increase fatty acid combustion in the liver tissue. In contrast, adiponectin has little effect on ritonavir-induced hypercholesterolemia and hepatic cholesterol synthesis. These results suggest that hypoadiponectinemia is partly responsible for the metabolic disorders induced by HIV PIs, and adiponectin or its agonists might be useful for the treatment of these disorders. |
| Databáze: | OpenAIRE |
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