Sphingolipid changes do not underlie fatty acid-evoked GLUT4 insulin resistance nor inflammation signals in muscle cells[S]
| Autor: | Philip J. Bilan, Zhi Liu, Maya R. Jacobson, Juleen R. Zierath, Paul L. Milligan, Scott Frendo-Cumbo, Joseph T. Brozinick, Nicolas J. Pillon, Hai Hoang Bui, Amira Klip |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Ceramide Glucose uptake Muscle Fibers Skeletal Palmitic Acid 030209 endocrinology & metabolism Inflammation QD415-436 Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Insulin resistance Internal medicine Myriocin glucose transporter 4 medicine Animals Research Articles Sphingolipids Glucose Transporter Type 4 ceramides biology Muscles Fatty Acids NF-kappa B Glucose transporter Cell Biology medicine.disease Sphingolipid Rats Protein Transport 030104 developmental biology chemistry inflammation biology.protein lipidomics Insulin Resistance medicine.symptom GLUT4 Signal Transduction |
| Zdroj: | Journal of Lipid Research, Vol 59, Iss 7, Pp 1148-1163 (2018) |
| ISSN: | 0022-2275 |
| DOI: | 10.1194/jlr.m080788 |
| Popis: | Ceramides contribute to obesity-linked insulin resistance and inflammation in vivo, but whether this is a cell-autonomous phenomenon is debated, particularly in muscle, which dictates whole-body glucose uptake. We comprehensively analyzed lipid species produced in response to fatty acids and examined the consequence to insulin resistance and pro-inflammatory pathways. L6 myotubes were incubated with BSA-adsorbed palmitate or palmitoleate in the presence of myriocin, fenretinide, or fumonisin B1. Lipid species were determined by lipidomic analysis. Insulin sensitivity was scored by Akt phosphorylation and glucose transporter 4 (GLUT4) translocation, while pro-inflammatory indices were estimated by IκBα degradation and cytokine expression. Palmitate, but not palmitoleate, had mild effects on Akt phosphorylation but significantly inhibited insulin-stimulated GLUT4 translocation and increased expression of pro-inflammatory cytokines Il6 and Ccl2. Ceramides, hexosylceramides, and sphingosine-1-phosphate significantly heightened by palmitate correlated negatively with insulin sensitivity and positively with pro-inflammatory indices. Inhibition of sphingolipid pathways led to marked changes in cellular lipids, but did not prevent palmitate-induced impairment of insulin-stimulated GLUT4 translocation, suggesting that palmitate-induced accumulation of deleterious lipids and insulin resistance are correlated but independent events in myotubes. We propose that muscle cell-endogenous ceramide production does not evoke insulin resistance and that deleterious effects of ceramides in vivo may arise through ancillary cell communication. |
| Databáze: | OpenAIRE |
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