Intramyocellular ceramides: subcellular concentrations and fractional de novo synthesis in postabsorptive humans
Open accessAbstract
We investigated the relationship between insulin resistance markers and subsarcolemmal (SS) and intramyofibrillar (IMF) ceramide concentrations, as well as the contribution of plasma palmitate (6.5-h infusion of [U-13C]palmitate) to intramyocellular ceramides. Seventy-six postabsorptive men and women had muscle biopsies 1.5, 6.5, and 24 h after starting the tracer infusion. Concentrations and enrichment of muscle ceramides were measured by liquid chromatography-tandem mass spectrometry. We found that HOMA of insulin resistance, plasma insulin, and triglyceride concentrations were positively correlated with SS C16:0 and C18:1 ceramide, but not SS C14:0-Cer, C20:0-Cer, C24:0-Cer, and C24:1-Cer concentrations; IMF ceramide concentrations were not correlated with any metabolic parameters. The fractional contribution of plasma palmitate to 16:0 ceramide was greater in SS than IMF (SS, 18.2% vs. IMF, 8.7%; P = 0.0006). Plasma insulin concentrations correlated positively with the fractional contribution of plasma palmitate to SS 16:0 ceramide. The fractional contribution of plasma palmitate to intramyocellular SS 16:0 ceramide was positively correlated with SS C16:0 ceramide concentrations (γ = 0.435; P = 0.002). We conclude that skeletal muscle SS ceramides, especially C16 to C18 chain lengths and the de novo synthesis of intramyocellular ceramide from plasma palmitate are associated with markers of insulin resistance.
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Different approaches for the measurement of ceramide synthesis in vivo have been proposed, e.g. infusion of U13C palmitate as ceramide precursors in humans to measure de novo synthesis in skeletal muscle or labelled palmitate to measure hepatic ceramide kinetics in rat models.
“Different approaches for the measurement of ceramide synthesis in vivo have been proposed, e.g. the infusion of U13C palmitate as ceramide precursors, used in humans to measure de novo synthesis of ceramides in skeletal muscle[119], [120], [121] or labelled palmitate used to measure hepatic ceramide kinetics in rat models.122,123”
From Lipid metabolism in MASLD and MASH: From mechanism to the clinic (2024) · cites this paper as [121]
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- Authors
- Chung, J. O., Koutsari, C., Blachnio-Zabielska, A. U., Hames, K. C., & Jensen, M. D.
- Affiliations
- Chonnam National University (KR)
- Mayo Clinic (US)
- Department of Hygiene, Epidemiology and Metabolic Disorders, Medical University of Białystok, Białystok, Poland
- Corresponding author
- Jensen, Michael D.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2017-05-08
- Volume
- 66
- Issue
- 8
- Pages
- 2082-2091
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC5521869
- OpenAlex
- W2613259577
- Cited by
- 45
- References
- 37
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 8 · 2019: 3 · 2018: 10 · 2017: 3
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (DK-40484, DK-45343, DK-50456, R-00585)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- insulin resistance, de novo ceramide synthesis, skeletal muscle, HOMA-IR, postabsorptive state
- MeSH terms
- Adult, Biopsy, Ceramides, Chromatography, Liquid, Fasting, Fatty Acids, Nonesterified, Female, Humans, Insulin, Insulin Resistance, Male, Myofibrils, Palmitates, Sarcolemma, Time Factors, Triglycerides, Muscle, Skeletal, Muscle Cells, Tandem Mass Spectrometry, Healthy Volunteers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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