Trial reportJCI insight2018
Intracellular localization of diacylglycerols and sphingolipids influences insulin sensitivity and mitochondrial function in human skeletal muscle.
Trial report in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 3 of them syntheses 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.
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
107 citing papers in PubMed, 3 syntheses or guidelines pooled it, 175 citations in OpenAlex.
- Pooled it
- The Effect of High-Fat Diet on Intramyocellular Lipid Content in Healthy Adults: A Systematic Review, Meta-Analysis, and Meta-Regression.The Journal of nutrition · 2024Pooled it
- The crucial role and mechanism of insulin resistance in metabolic disease.Frontiers in endocrinology · 2023Pooled it
- Determinants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals.Science advances · 2025Trial
- Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes.Nature communications · 2024Trial
- Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle.Diabetologia · 2022Trial
- Moderate-Intensity Exercise and High-Intensity Interval Training Affect Insulin Sensitivity Similarly in Obese Adults.The Journal of clinical endocrinology and metabolism · 2020Trial
- Skeletal muscle ceramides and relationship with insulin sensitivity after 2 weeks of simulated sedentary behaviour and recovery in healthy older adults.The Journal of physiology · 2018Trial
- Exercise and Fat: A Primer.Sports medicine - open · 2026Review
- Article
- Fibre morphology, intramyocellular lipid content and 3D capillary architecture in human postural, respiratory and locomotor muscles in type 2 diabetes mellitus.Histochemistry and cell biology · 2026Article
- Ceramide metabolism in oxidative and glycolytic muscle: Significance for lipid-induced insulin resistance.Molecular metabolism · 2026Article
- Detergents without a drain: the evolutionary logic (and liability) of sphingolipids.Journal of lipid research · 2026Review
- The transition from preclinical to clinical obesity: the importance of a borderline stage.Clinical science (London, England : 1979) · 2026Review
- Myosteatosis in type 1 diabetes: immunometabolic mechanisms, biomarkers, and therapeutic targets.Frontiers in endocrinology · 2026Review
- The "Mechano-Metabolic-Immune" crosstalk within the skeletal muscle microenvironment: evolution of homeostatic remodeling and quality control mechanisms.Frontiers in immunology · 2026Review
- Organelle-specific lipid profiles influence/underlie metabolic health in a nutrition-dependent manner.bioRxiv : the preprint server for biology · 2025Article
- Article
- Dietary sphingolipids and milk fat globule membrane: emerging roles in cardiometabolic health and muscle function.Food science and biotechnology · 2025Review
- Skeletal muscle atrophy and dysfunction in obesity and type-2 diabetes mellitus: Myocellular mechanisms involved.Reviews in endocrine & metabolic disorders · 2025Review
47 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
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAccumulation of diacylglycerol (DAG) and sphingolipids is thought to promote skeletal muscle insulin resistance by altering cellular signaling specific to their location. However,the subcellular localization of bioactive lipids in human skeletal muscle is largely unknown.
methodsWe evaluated subcellular localization of skeletal muscle DAGs and sphingolipids in lean individuals (n = 15), endurance-trained athletes (n = 16), and obese men and women with (n = 12) and without type 2 diabetes (n = 15). Muscle biopsies were fractionated into sarcolemmal, cytosolic, mitochondrial/ER, and nuclear compartments. Lipids were measured using liquid chromatography tandem mass spectrometry, and insulin sensitivity was measured using hyperinsulinemic-euglycemic clamp.
resultsSarcolemmal 1,2-DAGs were not significantly related to insulin sensitivity. Sarcolemmal ceramides were inversely related to insulin sensitivity, with a significant relationship found for the C18:0 species. Sarcolemmal sphingomyelins were also inversely related to insulin sensitivity, with the strongest relationships found for the C18:1, C18:0, and C18:2 species. In the mitochondrial/ER and nuclear fractions, 1,2-DAGs were positively related to, while ceramides were inversely related to, insulin sensitivity. Cytosolic lipids as well as 1,3-DAG, dihydroceramides, and glucosylceramides in any compartment were not related to insulin sensitivity. All sphingolipids but only specific DAGs administered to isolated mitochondria decreased mitochondrial state 3 respiration.
conclusionThese data reveal previously unknown differences in subcellular localization of skeletal muscle DAGs and sphingolipids that relate to whole-body insulin sensitivity and mitochondrial function in humans. These data suggest that whole-cell concentrations of lipids obscure meaningful differences in compartmentalization and suggest that subcellular localization of lipids should be considered when developing therapeutic interventions to treat insulin resistance.
fundingNational Institutes of Health General Clinical Research Center (RR-00036), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01DK089170), NIDDK (T32 DK07658), and Colorado Nutrition Obesity Research Center (P30DK048520).
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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.