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Related Experiment Videos

Cell-permeable ceramides increase basal glucose incorporation into triacylglycerols but decrease the stimulation by

J Mei1, C-N Wang, L O'Brien

  • 1Department of Biochemistry (Signal Transduction Research Group), University of Alberta, Edmonton, Alberta, Canada.

International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity
|January 18, 2003
PubMed
Summary

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Ceramides mimic tumor necrosis factor-alpha (TNFalpha) effects, causing insulin resistance. However, they also promote glucose uptake and fat storage in adipocytes, explaining aspects of obesity and insulin resistance.

Area of Science:

  • Cellular and Molecular Biology
  • Metabolic Research
  • Endocrinology

Background:

  • Ceramides are bioactive lipids mediating cellular responses.
  • Tumor necrosis factor-alpha (TNFalpha) induces insulin resistance.
  • Understanding ceramide regulation of glucose metabolism is crucial for metabolic disease research.

Purpose of the Study:

  • To investigate how ceramides regulate glucose incorporation into triacylglycerols in adipocytes.
  • To elucidate the role of ceramides in mediating TNFalpha-induced insulin resistance.
  • To explore the signaling pathways involved in ceramide action on adipocyte metabolism.

Main Methods:

  • Utilized 3T3-L1 adipocytes for in vitro studies.
  • Administered cell-permeable ceramides (C2- and C6-ceramides).

Related Experiment Videos

  • Measured glucose uptake, triacylglycerol synthesis, and key signal transduction pathway activations (PI3K, S6K, MAPK, Akt).

    • Main Results:

    • C6-ceramide altered basal and insulin-stimulated glucose uptake.
    • C2-ceramide increased glucose incorporation into triacylglycerols, particularly the glycerol moiety, via GLUT1 synthesis.
    • Ceramides activated multiple signaling kinases but also impaired insulin-stimulated pathways.

    Conclusions:

    • Cell-permeable ceramides can replicate TNFalpha's insulin-sensitizing effects.
    • Ceramides induce long-term adaptations in adipocytes for glucose uptake and triacylglycerol storage independent of insulin.
    • These findings offer insights into TNFalpha-induced insulin resistance and fat accumulation in obesity.