ArticleNature metabolism2020
The PI3K pathway preserves metabolic health through MARCO-dependent lipid uptake by adipose tissue macrophages.
Article in Nature metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
21 citing papers in PubMed, 41 citations in OpenAlex.
- Valvular Leaflets Are Not Innocent Bystanders: Divergent Fibrotic Remodeling Accompanies Functional Mitral and Tricuspid Regurgitation.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- TREM2 promotes adipogenesis of PDGFR-αFrontiers in endocrinology · 2026Article
- Lipid-Associated Macrophages in Obesity: Immunometabolic Programs and Emerging Therapeutic Implications-A Narrative Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Targeting MARCO in combination with anti-CTLA-4 leads to enhanced melanoma regression and immune cell infiltration via macrophage reprogramming.Journal for immunotherapy of cancer · 2025Article
- Therapeutic targeting of white adipose tissue metabolic dysfunction in obesity: mechanisms and opportunities.MedComm · 2024Review
- Aberrant Lipid Metabolism in Macrophages Is Associated with Granuloma Formation in Sarcoidosis.American journal of respiratory and critical care medicine · 2024Article
- The application of MARCO for immune regulation and treatment.Molecular biology reports · 2024Review
- Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study.Journal of the American Heart Association · 2023Article
- Dietary fat and lipid metabolism in the tumor microenvironment.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Review
- Aqueous extract of Platycodon grandiflorus attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling.Chinese medicine · 2023Article
- Adipose tissue aging is regulated by an altered immune system.Frontiers in immunology · 2023Review
- Regulatory mechanisms of macrophage polarization in adipose tissue.Frontiers in immunology · 2023Review
- Superenhancer drives a tumor-specific splicing variant of MARCO to promote triple-negative breast cancer progression.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Interplay between fat cells and immune cells in bone: Impact on malignant progression and therapeutic response.Pharmacology & therapeutics · 2022Review
- Early macrophage response to obesity encompasses Interferon Regulatory Factor 5 regulated mitochondrial architecture remodelling.Nature communications · 2022Article
- Targeting macrophages in hematological malignancies: recent advances and future directions.Journal of hematology & oncology · 2022Review
- Role of adipose tissue macrophages in obesity-related disorders.The Journal of experimental medicine · 2022Article
- Reciprocal signaling between adipose tissue depots and the central nervous system.Frontiers in cell and developmental biology · 2022Review
- Adipoclast: a multinucleated fat-eating macrophage.BMC biology · 2021Review
Corrections and comments
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Authors and funding
28 authors at 8 institutions in 5 countries.
Funding
Abstract
Adipose tissue macrophages (ATMs) display tremendous heterogeneity depending on signals in their local microenvironment and contribute to the pathogenesis of obesity. The phosphoinositide 3-kinase (PI3K) signalling pathway, antagonized by the phosphatase and tensin homologue (PTEN), is important for metabolic responses to obesity. We hypothesized that fluctuations in macrophage-intrinsic PI3K activity via PTEN could alter the trajectory of metabolic disease by driving distinct ATM populations. Using mice harbouring macrophage-specific PTEN deletion or bone marrow chimeras carrying additional PTEN copies, we demonstrate that sustained PI3K activity in macrophages preserves metabolic health in obesity by preventing lipotoxicity. Myeloid PI3K signalling promotes a beneficial ATM population characterized by lipid uptake, catabolism and high expression of the scavenger macrophage receptor with collagenous structure (MARCO). Dual MARCO and myeloid PTEN deficiencies prevent the generation of lipid-buffering ATMs, reversing the beneficial actions of elevated myeloid PI3K activity in metabolic disease. Thus, macrophage-intrinsic PI3K signalling boosts metabolic health by driving ATM programmes associated with MARCO-dependent lipid uptake.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.