ArticleThe Journal of clinical investigation2011
Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 392 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
392 citing papers in PubMed, 2 syntheses or guidelines pooled it, 678 citations in OpenAlex.
- Tools for investigating O-GlcNAc in signaling and other fundamental biological pathways.The Journal of biological chemistry · 2024Pooled it
- The Role of Fatty Acids in Ceramide Pathways and Their Influence on Hypothalamic Regulation of Energy Balance: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Machine learning reveals serum sphingolipids as cholesterol-independent biomarkers of coronary artery disease.The Journal of clinical investigation · 2020Trial
- Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars.Diabetes care · 2018Trial
- Article
- Mechanism of Cinnamaldehyde in AlleviatingAnimals : an open access journal from MDPI · 2026Article
- Discovery of circadian clock activators with anti-obesity efficacy via suppression of adipocyte development and hypertrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Adipose Tissue-Central Nervous System Axis in Obesity: Molecular Mechanisms, Inflammation, and Nutritional and Technological Implications.Metabolites · 2026Review
- Cyclic Altitude Training, Mitochondrial Health, and the Oral-Airway Axis: Intermittent Hypoxia Between Adaptation and Disease.Journal of clinical medicine · 2026Review
- Maternal Microbiome in Gestational Diabetes Mellitus: Mechanisms, Biomarkers, and Therapeutic Perspectives.Life (Basel, Switzerland) · 2026Review
- Personalized Combination of a Ketogenic Diet and Low-Dose Semaglutide for Cardiometabolic Health: A Retrospective Case Series.Journal of personalized medicine · 2026Article
- Ceramide in Type 2 Diabetes and Obesity: Modulation by Nutrients and Dietary Patterns and Opportunities to Prevent and/or Manage Metabolic-Related Conditions.Metabolites · 2026Review
- Innate immune signalling in the adipocyte.Journal of biochemistry · 2026Review
- Sphingolipids in human disease: organ-specific pathologies, chain-length-dependent effects, and translational implications.Journal of translational medicine · 2026Review
- Detergents without a drain: the evolutionary logic (and liability) of sphingolipids.Journal of lipid research · 2026Review
- The Acid sphingomyelinase/ceramide System in Idiopathic Inflammatory Myopathies: a Potential Treatment Target.Inflammation · 2026Review
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- Dietary bioactive compounds targeting insulin resistance: mechanisms and preventive potential.Frontiers in nutrition · 2026Review
- Lipid-derived microbial metabolites at the gut-liver interface: regulation of intestinal barrier function, immune signaling, and metabolic inflammation.Frontiers in physiology · 2026Review
- Development and comparative evaluation of machine learning algorithms and Cox regression for predicting fasting plasma glucose-defined incident prediabetes: a longitudinal cohort study.Frontiers in endocrinology · 2026Article
332 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
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Obesity is associated with an enhanced inflammatory response that exacerbates insulin resistance and contributes to diabetes, atherosclerosis, and cardiovascular disease. One mechanism accounting for the increased inflammation associated with obesity is activation of the innate immune signaling pathway triggered by TLR4 recognition of saturated fatty acids, an event that is essential for lipid-induced insulin resistance. Using in vitro and in vivo systems to model lipid induction of TLR4-dependent inflammatory events in rodents, we show here that TLR4 is an upstream signaling component required for saturated fatty acid-induced ceramide biosynthesis. This increase in ceramide production was associated with the upregulation of genes driving ceramide biosynthesis, an event dependent of the activity of the proinflammatory kinase IKKβ. Importantly, increased ceramide production was not required for TLR4-dependent induction of inflammatory cytokines, but it was essential for TLR4-dependent insulin resistance. These findings suggest that sphingolipids such as ceramide might be key components of the signaling networks that link lipid-induced inflammatory pathways to the antagonism of insulin action that contributes to diabetes.
Indexed as
Identifiers
What OpenQuestion holds
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.