ArticleCells2022
Inhibition of Adipose Tissue Beiging by HIV Integrase Inhibitors, Dolutegravir and Bictegravir, Is Associated with Adipocyte Hypertrophy, Hypoxia, Elevated Fibrosis, and Insulin Resistance in Simian Adipose Tissue and Human Adipocytes.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Thermogenic Differentiation of Human Adipocyte Precursors in Culture: A Systematic Review.Cells · 2025Pooled it
- A distinct form of fat fibrosis is linked to insulin resistance in people with HIV.JCI insight · 2026Observational
- Association Between Different Antiretroviral Therapy Regimens and Adipokine Secretion Profile in HIV-Infected Individuals.International journal of molecular sciences · 2026Article
- Article
- Semi-automated, evidence-based workflow for selection of reference chemicals for the validation of NAMs: a case study with the adipogenesis assay.NAM journal · 2026Article
- Metabolic dysfunction-associated steatotic liver disease in people living with HIV: mechanisms, diagnosis, and management.Frontiers in immunology · 2026Review
- Combined tenofovir, lamivudine, and dolutegravir treatment increases leptin and FABP4 expression in human subcutaneous adipose tissue.Einstein (Sao Paulo, Brazil) · 2026Article
- Protective association of theFrontiers in medicine · 2026Article
- Article
- Lipodystrophy in HIV: Evolving Challenges and Unresolved Questions.International journal of molecular sciences · 2025Review
- Associations between weight gain, integrase inhibitors antiretroviral agents, and gut microbiome in people living with HIV: a cross-sectional study.Scientific reports · 2025Article
- Effect of dolutegravir-based antiretroviral therapy on glycemic control in female mice.Scientific reports · 2025Article
- Tenofovir alafenamide promotes weight gain and impairs fatty acid metabolism-related signaling pathways in visceral fat tissue compared to tenofovir disoproxil fumarate.Antiviral research · 2025Article
- Low-Level Viremia as an Independent Risk Factor for Metabolic Syndrome in People Living with HIV Receiving Antiretroviral Therapy: A 6-Year Retrospective Cohort Study.Infection and drug resistance · 2025Article
- Development and validation of a nomogram for predicting the outcome of metabolic syndrome among people living with HIV after antiretroviral therapy in China.Frontiers in cellular and infection microbiology · 2025Article
- Metabolic Complications Associated with Use of Integrase Strand Transfer Inhibitors (InSTI) for the Treatment of HIV-1 Infection: Focus on Weight Changes, Lipids, Glucose and Bone Metabolism.Current HIV/AIDS reports · 2024Review
- Weight Gain in HIV Adults Receiving Antiretroviral Treatment: Current Knowledge and Future Perspectives.Life (Basel, Switzerland) · 2024Review
- Effect of metabolic status on response to SIV infection and antiretroviral therapy in nonhuman primates.JCI insight · 2024Article
- Adipose Tissue Dysfunction and Energy Balance Paradigms in People Living With HIV.Endocrine reviews · 2024Review
- Cardiometabolic Health in Pregnancy and Postpartum: Findings From a Prospective Cohort Study in South Africa.Open forum infectious diseases · 2024Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For people living with HIV, treatment with integrase-strand-transfer-inhibitors (INSTIs) can promote adipose tissue (AT) gain. We previously demonstrated that INSTIs can induce hypertrophy and fibrosis in AT of macaques and humans. By promoting energy expenditure, the emergence of beige adipocytes in white AT (beiging) could play an important role by limiting excess lipid storage and associated adipocyte dysfunction. We hypothesized that INSTIs could alter AT via beiging inhibition. Fibrosis and gene expression were measured in subcutaneous (SCAT) and visceral AT (VAT) from SIV-infected, dolutegravir-treated (SIVART) macaques. Beiging capacity was assessed in human adipose stromal cells (ASCs) undergoing differentiation and being exposed to dolutegravir, bictegravir, or raltegravir. Expression of beige markers, such as positive-regulatory-domain-containing-16 (PRDM16), were lower in AT of SIVART as compared to control macaques, whereas fibrosis-related genes were higher. Dolutegravir and bictegravir inhibited beige differentiation in ASCs, as shown by lower expression of beige markers and lower cell respiration. INSTIs also induced a hypertrophic insulin-resistant state associated with a pro-fibrotic phenotype. Our results indicate that adipocyte hypertrophy induced by INSTIs is involved via hypoxia (revealed by a greater hypoxia-inducible-factor-1-alpha gene expression) in fat fibrosis, beiging inhibition, and thus (via positive feedback), probably, further hypertrophy and associated insulin resistance.
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Registered trials
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