ArticleCell metabolism2012
Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility.
Article in Cell metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 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
220 citing papers in PubMed, 2 syntheses or guidelines pooled it, 371 citations in OpenAlex.
- Association of maternal gut microbial metabolites with gestational diabetes mellitus: evidence from an original case-control study, meta-analysis, and Mendelian randomization.European journal of clinical nutrition · 2025Pooled it
- L-Carnitine's Effect on the Biomarkers of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Nutrients · 2020Pooled it
- Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness.Scientific reports · 2022Trial
- Moderate-Intensity Exercise and High-Intensity Interval Training Affect Insulin Sensitivity Similarly in Obese Adults.The Journal of clinical endocrinology and metabolism · 2020Trial
- L-carnitine infusion does not alleviate lipid-induced insulin resistance and metabolic inflexibility.PloS one · 2020Trial
- Trial
- Protein ingestion acutely inhibits insulin-stimulated muscle carnitine uptake in healthy young men.The American journal of clinical nutrition · 2016Trial
- Perilipin 3 Differentially Regulates Skeletal Muscle Lipid Oxidation in Active, Sedentary, and Type 2 Diabetic Males.The Journal of clinical endocrinology and metabolism · 2015Trial
- Defects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training.Diabetes · 2015Trial
- Increased missense mutation burden of Fatty Acid metabolism related genes in nunavik inuit population.PloS one · 2015Trial
- Mitochondrial membrane lipid cardiolipin controls fiber-type adaptations in aging muscle via estrogen-related receptor γ.Nature aging · 2026Article
- Differential activation of TCA cycle activity and PDH flux by dichloroacetate in skeletal muscle measured by hyperpolarized [2-iScience · 2026Article
- From Collapse to Active Self-Repair: Integrative Multi-Omics and Machine Learning Analysis Map the Hepatic Metabolic Adaption in Response to Simulated Spaceflight Stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Peroxisomes orchestrate metabolic flexibility and longevity via an interorganelle cascade.Nature aging · 2026Article
- Investigating the potential role of propionylcarnitine in milk pentadecanoic acid synthesis in Chinese holstein dairy cows using multi-omics analysis.BMC genomics · 2026Article
- FN3K deficiency drives tubular injury in diabetic kidney disease through impaired mitochondrial respiratory chain function.Frontiers in endocrinology · 2026Article
- Multi-omics reveals FAT10 as an immunometabolic survival factor rewiring global metabolism in cancer.Cell communication and signaling : CCS · 2025Article
- Oral octanoylcarnitine alleviates exercise intolerance in mouse models of long-chain fatty acid oxidation disorders.JCI insight · 2025Article
- Metabolic alterations associated with epileptic seizures detected by NMR spectroscopy.Scientific reports · 2025Article
- Early Sepsis Metabolic Changes in Kidney and Liver Precede Clinical Evidence of Organ Dysfunction.American journal of respiratory cell and molecular biology · 2025Article
160 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
16 authors at 2 institutions in 1 country.
Funding
Abstract
The concept of "metabolic inflexibility" was first introduced to describe the failure of insulin-resistant human subjects to appropriately adjust mitochondrial fuel selection in response to nutritional cues. This phenomenon has since gained increasing recognition as a core component of the metabolic syndrome, but the underlying mechanisms have remained elusive. Here, we identify an essential role for the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT), in regulating substrate switching and glucose tolerance. By converting acetyl-CoA to its membrane permeant acetylcarnitine ester, CrAT regulates mitochondrial and intracellular carbon trafficking. Studies in muscle-specific Crat knockout mice, primary human skeletal myocytes, and human subjects undergoing L-carnitine supplementation support a model wherein CrAT combats nutrient stress, promotes metabolic flexibility, and enhances insulin action by permitting mitochondrial efflux of excess acetyl moieties that otherwise inhibit key regulatory enzymes such as pyruvate dehydrogenase. These findings offer therapeutically relevant insights into the molecular basis of metabolic inflexibility.
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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.