The Role of Protease Inhibitors in the Pathogenesis of HIV-Associated Lipodystrophy: Cellular Mechanisms and Clinical Implications
| Autor: | Phillip B. Hylemon, Kevin E. Yarasheski, Paul W. Hruz, Mustafa A. Noor, Aouatef Bellamine, Rex A. Parker, Donald P. Kotler, Oliver P. Flint |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Adipose tissue HIV Infections Biology Toxicology Article Pathology and Forensic Medicine chemistry.chemical_compound Insulin resistance Insulin-Secreting Cells Internal medicine Adipocyte Adipocytes medicine Animals Humans Insulin HIV Protease Inhibitor Molecular Biology Lipoatrophy Cells Cultured Dyslipidemias Metabolic Syndrome HIV-Associated Lipodystrophy Syndrome HIV Protease Inhibitors Cell Biology medicine.disease Glucose Endocrinology Adipose Tissue Lipotoxicity chemistry Insulin Resistance Lipodystrophy |
| Zdroj: | Toxicologic Pathology. 37:65-77 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623308327119 |
| Popis: | Metabolic complications associated with HIV infection and treatment frequently present as a relative lack of peripheral adipose tissue associated with dyslipidemia and insulin resistance. In this review we explain the connection between abnormalities of intermediary metabolism, observed either in vitro or in vivo, and this group of metabolic effects. We review molecular mechanisms by which the HIV protease inhibitor (PI) class of drugs may affect the normal stimulatory effect of insulin on glucose and fat storage. We then propose that both chronic inflammation from HIV infection and treatment with some drugs in this class trigger cellular homeostatic stress responses with adverse effects on intermediary metabolism. The physiologic outcome is such that total adipocyte storage capacity is decreased, and the remaining adipocytes resist further fat storage. The excess circulating and dietary lipid metabolites, normally “absorbed” by adipose tissue, are deposited ectopically in lean (muscle and liver) tissue, where they impair insulin action. This process leads to a pathologic cycle of lipotoxicity and lipoatrophy and a clinical phenotype of body fat distribution with elevated waist-to-hip ratio similar to the metabolic syndrome. |
| Databáze: | OpenAIRE |
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