ArticleeLife2022
Enriched dietary saturated fatty acids induce trained immunity via ceramide production that enhances severity of endotoxemia and clearance of infection.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 56 citations in OpenAlex.
- Trained immunity in chronic, relapsing and low-grade joint inflammation.Nature reviews. Rheumatology · 2026Review
- Review
- Pro- and Anti-Inflammatory Macrophages Adjust UCP2 Protein Levels Based on Their Intrinsic Metabolism and Available Metabolites.European journal of immunology · 2026Article
- Dietary Saturated Fatty Acids as Evolutionarily Conserved Signals of Immune Activation.DNA and cell biology · 2026Review
- Dysregulation of macrophage lipid metabolism underlies intracellular bacterial neuroinvasion.Nature communications · 2026Article
- Review
- Recent perspectives on macrophage memory: types, mechanisms, and characteristics in pulmonary diseases.Cell communication and signaling : CCS · 2026Review
- Adipose tissue ceramides: emerging lipid components of extracellular vesicles and their influence on metabolic dysregulation.Frontiers in endocrinology · 2026Review
- Sphingolipid Metabolism: A Pathological Hub Linking Lipid Dysregulation and Chronic Inflammation in Atherosclerotic Cardiovascular Disease.Journal of inflammation research · 2026Review
- The immunology of sepsis: translating new insights into clinical practice.Nature reviews. Nephrology · 2026Review
- Can Nuclear Imaging Detect Trained Immunity in Cardiovascular Disease?Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Bone Marrow Immunometabolic Remodeling in Osteoporosis: From Systemic Risk Factors to Precision Intervention.International journal of general medicine · 2026Review
- The long-term effect of metabolic bariatric surgery on innate immune cell phenotype and function.International journal of obesity (2005) · 2025Observational
- Review
- Mechanisms of Innate Immune Modulation by High-Fat Diet: Implications for Obesity and Asthma.Current allergy and asthma reports · 2025Review
- Molecular Mechanisms of Sepsis-Associated Acute Kidney Injury.Journal of the American Society of Nephrology : JASN · 2025Review
- Trained immunity induced by DAMPs and LAMPs in chronic inflammatory diseases.Experimental & molecular medicine · 2025Review
- A systems approach for elucidating the role of the microbiome in epigenetic cellular memory.mSystems · 2025Review
- Review
- Maladaptive trained immunity in viral infections.The Journal of clinical investigation · 2025Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Trained immunity is an innate immune memory response that is induced by a primary inflammatory stimulus that sensitizes monocytes and macrophages to a secondary pathogenic challenge, reprogramming the host response to infection and inflammatory disease. Dietary fatty acids can act as inflammatory stimuli, but it is unknown if they can act as the primary stimuli to induce trained immunity. Here we find mice fed a diet enriched exclusively in saturated fatty acids (ketogenic diet; KD) confer a hyper-inflammatory response to systemic lipopolysaccharide (LPS) and increased mortality, independent of diet-induced microbiome and hyperglycemia. We find KD alters the composition of the hematopoietic stem cell compartment and enhances the response of bone marrow macrophages, monocytes, and splenocytes to secondary LPS challenge. Lipidomics identified enhanced free palmitic acid (PA) and PA-associated lipids in KD-fed mice serum. We found pre-treatment with physiologically relevant concentrations of PA induces a hyper-inflammatory response to LPS in macrophages, and this was dependent on the synthesis of ceramide. In vivo, we found systemic PA confers enhanced inflammation and mortality in response to systemic LPS, and this phenotype was not reversible for up to 7 days post-PA-exposure. Conversely, we find PA exposure enhanced clearance of
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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.