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Cell-permeable ceramides increase basal glucose incorporation into triacylglycerols but decrease the stimulation by
1Department of Biochemistry (Signal Transduction Research Group), University of Alberta, Edmonton, Alberta, Canada.
Summary
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).
- 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.