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Related Experiment Video

Updated: Aug 30, 2025

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Serum dihydroceramides correlate with insulin sensitivity in humans and decrease insulin sensitivity in vitro.

Simona Zarini1, Joseph T Brozinick2, Karin A Zemski Berry1

  • 1Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Journal of Lipid Research
|August 28, 2022
PubMed
Summary
This summary is machine-generated.

Serum dihydroceramides, not ceramides, are elevated in obesity and type 2 diabetes (T2D), and directly impair insulin sensitivity. These findings highlight dihydroceramides as key biomarkers for metabolic health.

Keywords:
CVDT2Dcirculating ceramidesinsulin resistancelipidomicsmyotubeobesityserumsphingolipids

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Area of Science:

  • Metabolic disease research
  • Lipidomics and sphingolipid metabolism
  • Cardiovascular disease (CVD) risk factors

Background:

  • Serum ceramides (C16:0, C18:0) are associated with cardiovascular disease (CVD) risk and insulin resistance.
  • The precise mechanisms linking serum sphingolipids to insulin resistance remain incompletely understood.
  • Obesity and type 2 diabetes (T2D) are characterized by altered metabolic profiles, including lipid abnormalities.

Purpose of the Study:

  • To comprehensively quantify serum sphingolipids across a spectrum of insulin sensitivity.
  • To investigate the direct role of dihydroceramides in causing insulin resistance using in vitro models.

Main Methods:

  • Quantification of a wide array of serum sphingolipids in individuals with varying insulin sensitivity.
  • Statistical analysis correlating sphingolipid levels with insulin sensitivity as a continuous variable.
  • In vitro experiments administering dihydroceramides to primary myotubes to assess effects on insulin sensitivity.

Main Results:

  • Serum triglycerides were elevated in individuals with obesity and T2D compared to lean individuals and athletes.
  • Inverse relationships were observed between serum C18:0, C20:0, and C22:0 ceramides and insulin sensitivity.
  • Total serum dihydroceramides and specific species (especially C18:0) were significantly higher in individuals with obesity and T2D, showing a strong inverse correlation with insulin sensitivity.
  • In vitro administration of dihydroceramides to myotubes reduced insulin sensitivity without altering overall intracellular sphingolipid content.

Conclusions:

  • Serum dihydroceramides, rather than ceramides, are significantly elevated in obesity and T2D and are inversely associated with insulin sensitivity.
  • Dihydroceramides appear to directly induce insulin resistance in muscle cells.
  • Serum dihydroceramides represent important predictive biomarkers and potential therapeutic targets for insulin resistance.