ArticleMolecular endocrinology (Baltimore, Md.)2008
Human immunodeficiency virus (HIV)-1 viral protein R suppresses transcriptional activity of peroxisome proliferator-activated receptor {gamma} and inhibits adipocyte differentiation: implications for HIV-associated lipodystrophy.
Article in Molecular endocrinology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed.
- Adipokines, Weight Gain and Metabolic and Inflammatory Markers After Antiretroviral Therapy Initiation: AIDS Clinical Trials Group (ACTG) A5260s.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Liver-specific Expression of HIV-1 Viral Protein R Causes Hepatic Steatosis and Glucose Intolerance in Male Mice.Journal of the Endocrine Society · 2025Article
- From fat storage to immune hubs: the emerging role of adipocytes in coordinating the immune response to infection.The FEBS journal · 2025Review
- Pathophysiology and Clinical Management of Dyslipidemia in People Living with HIV: Sailing through Rough Seas.Life (Basel, Switzerland) · 2024Review
- Article
- Article
- Antiretroviral Therapy-Induced Dysregulation of Gene Expression and Lipid Metabolism in HIV+ Patients: Beneficial Role of Antioxidant Phytochemicals.International journal of molecular sciences · 2022Review
- HIV-1 Vpr suppresses expression of the thiazide-sensitive sodium chloride co-transporter in the distal convoluted tubule.PloS one · 2022Article
- Infections at the nexus of metabolic-associated fatty liver disease.Archives of toxicology · 2021Review
- Severe insulin resistance syndromes.The Journal of clinical investigation · 2021Review
- Tissue is the issue: how altruistic people with HIV are changing the HIV tissue reservoir landscape.Future virology · 2020Article
- HIV and antiretroviral therapy-related fat alterations.Nature reviews. Disease primers · 2020Review
- Comorbidities of HIV infection: role of Nef-induced impairment of cholesterol metabolism and lipid raft functionality.AIDS (London, England) · 2020Review
- Obesity and Fat Metabolism in Human Immunodeficiency Virus-Infected Individuals: Immunopathogenic Mechanisms and Clinical Implications.The Journal of infectious diseases · 2019Article
- Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence.Frontiers in microbiology · 2019Review
- The role of human dopamine transporter in NeuroAIDS.Pharmacology & therapeutics · 2018Review
- HIV Persistence in Adipose Tissue Reservoirs.Current HIV/AIDS reports · 2018Review
- Adipose Tissue T Cells in HIV/SIV Infection.Frontiers in immunology · 2018Review
- Immune reconstitution in ART treated, but not untreated HIV infection, is associated with abnormal beta cell function.PloS one · 2018Article
- Review
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Authors and funding
8 authors.
Funding
Abstract
HIV-1-infected patients may develop lipodystrophy and insulin resistance. We investigated the effect of the HIV-1 accessory protein viral protein R (Vpr) on the activity of the peroxisome proliferator-activating receptor-gamma (PPARgamma), a key regulator of adipocyte differentiation and tissue insulin sensitivity. We studied expression of PPARgamma-responsive reporter genes in 3T3-L1 mouse adipocytes. We investigated Vpr interaction with the PPAR/retinoid X receptor (RXR)-binding site of the c-Cbl-associating protein (CAP) gene using the chromatin immunoprecipitation assay as well as the interaction of Vpr and PPARgamma using coimmunoprecipitation. Finally, we studied the ability of exogenous Vpr protein to enter cultured adipocytes and retard differentiation. We found that Vpr suppressed PPARgamma-induced transactivation in both undifferentiated and differentiated 3T3-L1 cells. Transcriptional suppression by Vpr required an intact LXXLL coactivator motif. Vpr suppressed mRNA expression of PPARgamma-responsive genes in undifferentiated 3T3-L1 cells and associated with the PPAR/RXR-binding site located in the promoter region of the CAP gene. Vpr interacted with the ligand-binding domain of PPARgamma in an agonist-dependent fashion in vitro. Vpr delivered either by an expression plasmid or as protein added to media suppressed PPARgamma agonist-induced adipocyte differentiation, assessed as lipid accumulation and mRNA expression of the adipocyte differentiation marker adipocyte P2 in 3T3-L1 cells. In conclusion, circulating Vpr or, alternatively, Vpr produced as a consequence of direct infection of adipocytes could suppress in vivo differentiation of preadipocytes by acting as a corepressor of PPARgamma-mediated gene transcription. Vpr may alter sensitivity to insulin and thereby contribute to the development of lipodystrophy and insulin resistance observed in HIV-1-infected patients.
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