ArticleJournal of leukocyte biology2019
Frontline Science: Acyl-CoA synthetase 1 exacerbates lipotoxic inflammasome activation in primary macrophages.
Article in Journal of leukocyte biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 39 citations in OpenAlex.
- Inflammatory signalling in diabetic cardiomyopathy: molecular mechanisms and potential therapeutic strategies.Nature reviews. Cardiology · 2026Review
- Targeting NLRP3 inflammasome to mitigate chemotherapy-induced cardiotoxicity: advances in selective inhibitors and natural modulators.Molecular biology reports · 2026Review
- Metabolic Adaptation in Acute Ischemic Events: The Critical Role of Acyl-Coenzyme A Synthetase Family in Myocardial Infarction and Ischemic Stroke.Journal of the American Heart Association · 2026Review
- Identification of key mitochondria-related genes in necrotizing enterocolitis using single-cell hdWGCNA and experimental verification.Pediatric research · 2026Article
- Fatty acid metabolism and lipid channeling in macrophages: mechanisms of inflammation, resolution, and lipotoxicity.Frontiers in immunology · 2026Review
- Long-chain acyl-CoA synthetases: biological functions, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- Multitemporal single-cell profiling uncovers alveolar IL1βClinical and translational medicine · 2025Article
- Moxibustion ameliorates abnormal subchondral bone remodeling by promoting ACSL1-mediated autophagy to degrade NLRP3 in osteoarthritis.Chinese medicine · 2025Article
- Activated TBK1 promotes ACSL1-mediated microglia lipid droplet accumulation and neuroinflammation in Parkinson's disease.Journal of neuroinflammation · 2025Article
- Immunometabolic reprogramming in macrophages infected with active and dormantInfection and immunity · 2025Article
- From fat to fire: The lipid-inflammasome connection.Immunological reviews · 2025Review
- Type I IFN induces long-chain acyl-CoA synthetase 1 to generate a phosphatidic acid reservoir for lipotoxic saturated fatty acids.Journal of lipid research · 2025Article
- Article
- NLRP3 inflammasome in cardiovascular diseases: an update.Frontiers in immunology · 2025Review
- Functional multi-organelle units control inflammatory lipid metabolism of macrophages.Nature cell biology · 2024Article
- Diabetes Mellitus to Accelerated Atherosclerosis: Shared Cellular and Molecular Mechanisms in Glucose and Lipid Metabolism.Journal of cardiovascular translational research · 2024Review
- Identification and verification of disulfidptosis-related genes in sepsis-induced acute lung injury.Frontiers in medicine · 2024Article
- Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy.Med (New York, N.Y.) · 2023Article
- Macrophage immunometabolism in diabetes-associated atherosclerosis.Immunometabolism (Cobham, Surrey) · 2023Review
- Inflammasomes and Atherosclerosis: a Mixed Picture.Circulation research · 2023Review
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7 authors at 1 institution in 1 country.
Funding
Abstract
Obesity and diabetes are associated with macrophage dysfunction and increased NLRP3 inflammasome activation. Saturated fatty acids (FAs) are abundant in these metabolic disorders and have been associated with lysosome dysfunction and inflammasome activation in macrophages. However, the interplay between cellular metabolic pathways and lipid-induced toxicity in macrophages remains poorly understood. In this study, we investigated the role of the lipid metabolic enzyme long chain acyl-CoA synthetase (ACSL1) in primary macrophages. ACSL1 is upregulated in TLR4-activated macrophages via a TIR (toll/IL-1R) domain-containing adapter inducing IFN-β (TRIF)-dependent pathway, and knockout of this enzyme decreased NLRP3 inflammasome activation. The mechanism of this response was not related to inflammasome priming, lipid uptake, or endoplasmic reticulum (ER) stress generation. Rather, ACSL1 was associated with mitochondria where it modulated fatty acid metabolism. The development of lysosome damage with palmitate exposure likely occurs via the formation of intracellular crystals. Herein, we provide evidence that loss of ACSL1 in macrophages decreases FA crystal formation thereby reducing lysosome damage and IL-1β release. These findings suggest that targeting lipid metabolic pathways in macrophages may be a strategy to reduce lipotoxity and to decrease pathologic inflammation in metabolic disease.
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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.