ArticleProceedings of the National Academy of Sciences of the United States of America2018
SREBP-1a-stimulated lipid synthesis is required for macrophage phagocytosis downstream of TLR4-directed mTORC1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 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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Who cites it
76 citing papers in PubMed, 113 citations in OpenAlex.
- Dynamic metabolic programming of monocyte-derived cells defines immunity in CNS disease.Brain : a journal of neurology · 2026Review
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- Toll-like receptor 4 signaling links cytoskeletal remodeling to lipid accumulation in macrophages.Inflammation and regeneration · 2026Review
- Modulation and Reprogramming of Adipose Tissue Macrophages in Obesity.Biomolecules · 2026Review
- Dysregulation of the AMPK-SREBP1-FASN axis in MASLD: driving a vicious cycle of lipotoxicity and metabolic-immune crosstalk.Lipids in health and disease · 2026Review
- Hyperglycemia- induced innate immune tolerance involves the metabolic and epigenetic rewiring in human alveolar macrophages.Frontiers in immunology · 2026Article
- Reframing macrophage polarization through cholesterol efflux: an organelle-coupled immunometabolic model.Frontiers in immunology · 2026Review
- Fatty acid metabolism and lipid channeling in macrophages: mechanisms of inflammation, resolution, and lipotoxicity.Frontiers in immunology · 2026Review
- Coordinated inhibition of M1 macrophage polarization by FIT2-mediated lipid droplet biosynthesis and FABP5.Zoological research · 2025Article
- Metabolic Programming Drives Protective and Inflammatory Monocyte Fates in Viral Encephalitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- mTOR Signaling in Macrophages: All Depends on the Context.International journal of molecular sciences · 2025Review
- Higher levels of plasma phosphatidylcholine (17:0_18:1) raise the risk of developing Parkinson's disease.Scientific reports · 2025Article
- Article
- Therapeutic targeting of myeloid cells in liver fibrosis: Mechanisms and clinical prospects.Animal models and experimental medicine · 2025Review
- SREBF1 mediates immunoparalysis of dendritic cells in sepsis by regulating lipid metabolism and endoplasmic reticulum stress.Cell communication and signaling : CCS · 2025Article
- The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease.Cellular & molecular biology letters · 2025Review
- Metabolism Serves as a Bridge Between Cardiomyocytes and Immune Cells in Cardiovascular Diseases.Cardiovascular drugs and therapy · 2025Review
- The protective effect of higher serum TAG (51:4) levels against Parkinson's disease.The British journal of nutrition · 2025Article
- Adropin: a key player in immune cell homeostasis and regulation of inflammation in several diseases.Frontiers in immunology · 2025Review
- Lipin-1 restrains macrophage lipid synthesis to promote inflammation resolution.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
There is a growing appreciation for a fundamental connection between lipid metabolism and the immune response. Macrophage phagocytosis is a signature innate immune response to pathogen exposure, and cytoplasmic membrane expansion is required to engulf the phagocytic target. The sterol regulatory element binding proteins (SREBPs) are key transcriptional regulatory proteins that sense the intracellular lipid environment and modulate expression of key genes of fatty acid and cholesterol metabolism to maintain lipid homeostasis. In this study, we show that TLR4-dependent stimulation of macrophage phagocytosis requires mTORC1-directed SREBP-1a-dependent lipid synthesis. We also show that the phagocytic defect in macrophages from SREBP-1a-deficient mice results from decreased interaction between membrane lipid rafts and the actin cytoskeleton, presumably due to reduced accumulation of newly synthesized fatty acyl chains within major membrane phospholipids. We show that mTORC1-deficient macrophages also have a phagocytic block downstream from TLR4 signaling, and, interestingly, the reduced level of phagocytosis in both SREBP-1a- and mTORC1-deficient macrophages can be restored by ectopic SREBP-1a expression. Taken together, these observations indicate SREBP-1a is a major downstream effector of TLR4-mTORC1 directed interactions between membrane lipid rafts and the actin cytoskeleton that are required for pathogen-stimulated phagocytosis in macrophages.
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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.