ArticleThe Journal of biological chemistry2018
An unexpected link between fatty acid synthase and cholesterol synthesis in proinflammatory macrophage activation.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
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
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 186 citations in OpenAlex.
- The role of fatty acid metabolism in acute lung injury: a special focus on immunometabolism.Cellular and molecular life sciences : CMLS · 2024Pooled it
- Molecular Mechanisms and Therapeutic Targeting of the Macrophage Metabolic-Epigenetic Interaction Network in Chronic Obstructive Pulmonary Disease.Cell biochemistry and biophysics · 2026Review
- Macrophages tune NK cell IFNγ production through direct lipid transfer.Nature communications · 2026Article
- Phosphoproteomic Landscape of HDLBP: Insights into Function and Disease Associations.International journal of molecular sciences · 2026Article
- Acetylation of fatty acid synthase regulates microglial lipid droplets accumulation and pro-inflammatory activity following traumatic brain injury.Redox biology · 2026Article
- Choice of lipid supplementation for in vitro erythroid cell culture impacts reticulocyte yield and characteristics.Scientific reports · 2026Article
- Cholesterol Metabolism: An Ally in the Development and Progression of Cervical Cancer.International journal of molecular sciences · 2026Review
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Targeting macrophage metabolism: mechanisms, cellular crosstalk and implications in obesity-associated metabolic diseases.Frontiers in immunology · 2026Review
- Metabolic reprogramming of macrophages during mycobacterial infection: a review of immunometabolic crosstalk and pathogen manipulation.Frontiers in cellular and infection microbiology · 2026Review
- Fatty acid metabolism and lipid channeling in macrophages: mechanisms of inflammation, resolution, and lipotoxicity.Frontiers in immunology · 2026Review
- Genetically predicted immune cell mediate the association between plasma lipidomics and osteomyelitis.European journal of medical research · 2025Article
- Alterations in Lipid Metabolism and Hepatopancreatic Lipidomics Induced by Microcystin-LR Exposure in Common Carp (Animals : an open access journal from MDPI · 2025Article
- Maternal Hydroxytyrosol Supplementation Enhances Antioxidant Capacity and Immunometabolic Adaptations in Nutrient-Restricted Beef Cows and Their Offspring.Antioxidants (Basel, Switzerland) · 2025Article
- Maladaptive trained immunity in viral infections.The Journal of clinical investigation · 2025Review
- Review
- Lipids: Driving Forces in the Underlying Biology of Carcinogenesis.ACS pharmacology & translational science · 2025Review
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- Fatty acid synthase global inducible knockout does not alter brain fatty acid concentrations but attenuates cholesterol synthesis in the adult mouse.Prostaglandins, leukotrienes, and essential fatty acids · 2025Article
- Systems analysis unravels a common rural-urban gradient in immunological profile, function, and metabolic dependencies.Science advances · 2025Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Different immune activation states require distinct metabolic features and activities in immune cells. For instance, inhibition of fatty acid synthase (FASN), which catalyzes the synthesis of long-chain fatty acids, prevents the proinflammatory response in macrophages; however, the precise role of this enzyme in this response remains poorly defined. Consistent with previous studies, we found here that FASN is essential for lipopolysaccharide-induced, Toll-like receptor (TLR)-mediated macrophage activation. Interestingly, only agents that block FASN upstream of acetoacetyl-CoA synthesis, including the well-characterized FASN inhibitor C75, inhibited TLR4 signaling, while those acting downstream had no effect. We found that acetoacetyl-CoA could overcome C75's inhibitory effect, whereas other FASN metabolites, including palmitate, did not prevent C75-mediated inhibition. This suggested an unexpected role for acetoacetyl-CoA in inflammation that is independent of its role in palmitate synthesis. Our evidence further suggested that acetoacetyl-CoA arising from FASN activity promotes cholesterol production, indicating a surprising link between fatty acid synthesis and cholesterol synthesis. We further demonstrate that this process is required for TLR4 to enter lipid rafts and facilitate TLR4 signaling. In conclusion, we have uncovered an unexpected link between FASN and cholesterol synthesis that appears to be required for TLR signal transduction and proinflammatory macrophage activation.
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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 OpenQuestion graph.