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Regulation of glucose homeostasis and insulin action by ceramide acyl-chain length: A beneficial role for very long-chain sphingolipid species

Journal Article


Abstract


  • In a recent study, we showed that in response to high fat feeding C57BL/6, 129X1, DBA/2 and FVB/N mice all

    developed glucose intolerance, while BALB/c mice displayed minimal deterioration in glucose tolerance and

    insulin action. Lipidomic analysis of livers across these five strains has revealedmarked strain-specific differences

    in ceramide (Cer) and sphingomyelin (SM)specieswith high-fat feeding;with increases in C16-C22 (long-chain)

    and reductions in C N 22 (very long-chain) Cer and SM species observed in the four strains that developed HFDinduced

    glucose intolerance. Intriguingly, the opposite pattern was observed in sphingolipid species in BALB/c

    mice. These strain-specific changes in sphingolipid acylation closely correlated with ceramide synthase 2

    (CerS2) protein content and activity, with reduced CerS2 levels/activity observed in glucose intolerant strains

    and increased content in BALB/c mice. Overexpression of CerS2 in primary mouse hepatocytes induced a specific

    elevation in very long-chain Cer, but despite the overall increase in ceramide abundance, there was a substantial

    improvement in insulin signal transduction, as well as decreased ER stress and gluconeogenic markers. Overall

    our findings suggest that very long-chain sphingolipid species exhibit a protective role against the development

    of glucose intolerance and hepatic insulin resistance.

UOW Authors


  •   Montgomery, Magdalene K. (external author)
  •   Brown, Simon (external author)
  •   Lim, Xin Ying (external author)
  •   Fiveash, C E. (external author)
  •   Osborne, Brenna (external author)
  •   Bentley, Nicholas L. (external author)
  •   Braude, J P. (external author)
  •   Mitchell, Todd
  •   Coster, Adelle C. F. (external author)
  •   Don, Anthony S. (external author)
  •   Cooney, Gregory J. (external author)
  •   Schmitz-Peiffer, Carsten (external author)
  •   Turner, Nigel (external author)

Publication Date


  • 2016

Citation


  • Montgomery, M. K., Brown, S. H. J., Lim, X. Y., Fiveash, C. E., Osborne, B., Bentley, N. L., Braude, J. P., Mitchell, T. W., Coster, A. C. F., Don, A. S., Cooney, G. J., Schmitz-Peiffer, C. & Turner, N. (2016). Regulation of glucose homeostasis and insulin action by ceramide acyl-chain length: A beneficial role for very long-chain sphingolipid species. Biochimica Et Biophysica Acta-molecular And Cell Biology Of Lipids, 1861 (11), 1828-1839.

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/929

Number Of Pages


  • 11

Start Page


  • 1828

End Page


  • 1839

Volume


  • 1861

Issue


  • 11

Abstract


  • In a recent study, we showed that in response to high fat feeding C57BL/6, 129X1, DBA/2 and FVB/N mice all

    developed glucose intolerance, while BALB/c mice displayed minimal deterioration in glucose tolerance and

    insulin action. Lipidomic analysis of livers across these five strains has revealedmarked strain-specific differences

    in ceramide (Cer) and sphingomyelin (SM)specieswith high-fat feeding;with increases in C16-C22 (long-chain)

    and reductions in C N 22 (very long-chain) Cer and SM species observed in the four strains that developed HFDinduced

    glucose intolerance. Intriguingly, the opposite pattern was observed in sphingolipid species in BALB/c

    mice. These strain-specific changes in sphingolipid acylation closely correlated with ceramide synthase 2

    (CerS2) protein content and activity, with reduced CerS2 levels/activity observed in glucose intolerant strains

    and increased content in BALB/c mice. Overexpression of CerS2 in primary mouse hepatocytes induced a specific

    elevation in very long-chain Cer, but despite the overall increase in ceramide abundance, there was a substantial

    improvement in insulin signal transduction, as well as decreased ER stress and gluconeogenic markers. Overall

    our findings suggest that very long-chain sphingolipid species exhibit a protective role against the development

    of glucose intolerance and hepatic insulin resistance.

UOW Authors


  •   Montgomery, Magdalene K. (external author)
  •   Brown, Simon (external author)
  •   Lim, Xin Ying (external author)
  •   Fiveash, C E. (external author)
  •   Osborne, Brenna (external author)
  •   Bentley, Nicholas L. (external author)
  •   Braude, J P. (external author)
  •   Mitchell, Todd
  •   Coster, Adelle C. F. (external author)
  •   Don, Anthony S. (external author)
  •   Cooney, Gregory J. (external author)
  •   Schmitz-Peiffer, Carsten (external author)
  •   Turner, Nigel (external author)

Publication Date


  • 2016

Citation


  • Montgomery, M. K., Brown, S. H. J., Lim, X. Y., Fiveash, C. E., Osborne, B., Bentley, N. L., Braude, J. P., Mitchell, T. W., Coster, A. C. F., Don, A. S., Cooney, G. J., Schmitz-Peiffer, C. & Turner, N. (2016). Regulation of glucose homeostasis and insulin action by ceramide acyl-chain length: A beneficial role for very long-chain sphingolipid species. Biochimica Et Biophysica Acta-molecular And Cell Biology Of Lipids, 1861 (11), 1828-1839.

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/929

Number Of Pages


  • 11

Start Page


  • 1828

End Page


  • 1839

Volume


  • 1861

Issue


  • 11