Oleic and linoleic fatty acids downregulate Slc2a4/GLUT4 expression via NFKB and SREBP1 in skeletal muscle cells.
Oleic (OA) and linoleic (LA) fatty acids may be important regulators of Slc2a4 gene (GLUT4 protein) in skeletal muscle, thus participating in insulin resistance. We investigated the effect of OA and LA on the Slc2a4/GLUT4 expression in L6 muscle cells; as well as potential transcriptional regulators. OA and LA (50-400 µM) decreased the Slc2a4/GLUT4 expression in a dose-dependent way (maximum of ~50%, P < 0.001). OA and LA did not alter the Slc2a4-binding activity of oxysterols-receptor-LXR-alpha and peroxisome-proliferator-activated-receptor-gamma; but decreased the Slc2a4-binding activity of the sterol-regulatory-element-binding-protein-1 (SREBP1) enhancer (50%, P < 0.001), and increased (~30%, P < 0.001) the nuclear proteins binding into the Slc2a4-nuclear-factor-NF-kappa-B-binding site (repressor), and the phosphorylation of the inhibitors of nuclear-factor-kappa-B-kinase alpha/beta (150-300%, P < 0.001). In sum, OA and LA are potent inhibitors of the Slc2a4/GLUT4 expression in muscle cells; an effect involving reduced SREBP1 and increased NFKB transcriptional activity. These regulations may participate in the fatty acid-related pathophysiology of insulin resistance.
['Poletto|Ana Cláudia|AC|', 'Furuya|Daniela Tomie|DT|', 'David-Silva|Aline|A|', 'Ebersbach-Silva|Patrícia|P|', 'Santos|Camilo Lellis|CL|', 'Corrêa-Giannella|Maria Lúcia|ML|', 'Passarelli|Marisa|M|', 'Machado|Ubiratan Fabres|UF|']
D000818:Animals D002467:Cell Nucleus D002478:Cells, Cultured D015536:Down-Regulation D051275:Glucose Transporter Type 4 D019787:Linoleic Acid D032448:Myoblasts, Skeletal D016328:NF-kappa B D019301:Oleic Acid D011401:Promoter Regions, Genetic D051381:Rats D051780:Sterol Regulatory Element Binding Protein 1
Insulin resistance Electrophoretic mobility shift assay LXR-α PPAR-γ Transcription factors Unsaturated fatty acid