The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance.
Abstract
HIV-1 protease-inhibitor treatments are associated with a syndrome of peripheral lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidaemia, and insulin resistance. The catalytic region of HIV-1 protease, to which protease inhibitors bind, has approximately 60% homology to regions within two proteins that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein type 1 (CRABP-1) and low density lipoprotein-receptor-related protein (LRP). We hypothesise that protease inhibitors inhibit CRABP-1-modified, and cytochrome P450 3A-mediated synthesis of cis-9-retinoic acid, a key activator of the retinoid X receptor; and peroxisome proliferator activated receptor type gamma (PPAR-gamma) heterodimer, an adipocyte receptor that regulates peripheral adipocyte differentiation and apoptosis. Protease-inhibitor binding to LRP would impair hepatic chylomicron uptake and triglyceride clearance by the endothelial LRP-lipoprotein lipase complex. The resulting hyperlipidaemia contributes to central fat deposition (and in the breasts in the presence of oestrogen), insulin resistance, and, in susceptible individuals, type 2 diabetes. Understanding the syndrome's pathogenesis should lead to treatment strategies and to the design of protease inhibitors that do not cause this syndrome.
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“Acquired lipodystrophy can be seen in patients with HIV infection who are being treated with highly active antiretroviral therapy (99).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [99]
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Sorted by citations
Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents
(1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-128-12_part_2-199806151-00003 · Cited by 5,197
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Self-citation
Metadata
- Authors
- Carr, A., Samaras, K., Chisholm, D. J., & Cooper, D. A.
- Affiliations
- UNSW Sydney (AU)
- Garvan Institute of Medical Research (AU)
- Corresponding author
- Carr, Andrew
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 1998-06
- Volume
- 351
- Issue
- 9119
- Pages
- 1881-1883
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2171030070
- Cited by
- 1,065
- References
- 24
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 12 · 2023: 2 · 2022: 12 · 2021: 7 · 2020: 10 · 2019: 16 · 2018: 15 · 2017: 18 · 2016: 15 · 2015: 18 · 2014: 17 · 2013: 30 · 2012: 23
- FWCI
- 143.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Infectious Diseases › HIV-related health complications and treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- HIV-1 protease inhibitors, hyperlipidemia, insulin resistance, abdominal obesity, breast hypertrophy, LRP, retinoic acid synthesis, retinoid X receptor, PPARγ, adipogenesis, adipocyte apoptosis, lipoprotein lipase, type 2 diabetes
- MeSH terms
- Cytochrome P-450 Enzyme System, Diabetes Mellitus, Type 2, Female, Humans, Hyperlipidemias, Insulin Resistance, Lipodystrophy, Obesity, Receptors, Immunologic, HIV Protease Inhibitors, Sequence Homology, Amino Acid, Receptors, Retinoic Acid, Low Density Lipoprotein Receptor-Related Protein-1
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