Type 2 & other diabetes

Oxidised phosphatidylcholine induces sarcolemmal ceramide accumulation and insulin resistance in skeletal muscle

DiabetologiaPublished Mechanistic study

Authors' conclusion

These data suggest that circulating oxidised phosphatidylcholine species promote ceramide accumulation and decrease insulin sensitivity in muscle, help explain localised sphingolipid accumulation and muscle inflammatory response, and highlight oxidised phosphatidylcholine species as potential targets to combat insulin resistance.

Study context

Population
Individuals spanning the physiological range of insulin sensitivity (serum); rat L6 myotubes in vitrocross-sectional study
Participants
58 individuals
Outcome
Oxidised phosphatidylcholine, ceramide and insulin sensitivity
Methodological detailscross-sectional human serum study, in vitro rat L6 myotubes, LC-MS/MS
  • Cross-sectional human serum study
  • In vitro rat L6 myotubes
  • LC-MS/MS

Main finding

As reported in the abstract

  • Serum oxidised phosphatidylcholine elevated in obesity and T2D
  • Serum oxidised phosphatidylcholine inversely correlated with insulin sensitivity
  • Serum oxidised phosphatidylcholine positively correlated with muscle sarcolemmal C18:0 ceramide
  • POVPC increased total ceramide and dihydroceramide and decreased total sphingomyelin in L6 myotube sarcolemma, via de novo ceramide synthesis and sphingomyelinase activation
  • POVPC increased inflammatory signalling and caused insulin resistance in L6 myotubes

Original publication

Oxidised phosphatidylcholine induces sarcolemmal ceramide accumulation and insulin resistance in skeletal muscle. Diabetologia. Published 30 September 2024. doi:10.1007/s00125-024-06280-8

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