Endocrine Abstracts

Introduction: High circulating levels of some but not all unsaturated fatty acids (UFAs) can be related with reduced insulin sensitivity and glucose uptake in skeletal muscle. The real mechanisms by which UFAs impair the insulin sensitivity need to be clarified; nevertheless the UFA’s effects in the regulation of activity and/or expression of some transcriptional factors such as, nuclear factor κB (NFκB), hypoxia inducible factor-1a (HIF-1a), peroxisome proliferator-activated factor γ (PPARγ), liver-X-receptor alpha (LXR alpha) and sterol regulatory element binding protein 1c (SREBP-1c) which are related with SLC2A4 gene expression have been proposed. Therefore the aim of this study is to investigate the modulation SLC2A4 gene expression by oleic (OFA) (C18:1) and linoleic (LFA) (C18:2) unsaturated fatty acids. At the present moment the involvement of NFkappaB and HIF-1a in this mechanism has been analyzed.

Methods: L6 muscle cells were maintained in medium DMEM with BSA 1% and exposed to OFA (12.5–400 μM) and LFA (50–400 μM) for 16 h. GLUT4 protein content was analyzed by western blotting; mRNA expression by real time-PCR; NFκB and HIF-1a activation by gel shift.

Results: The GLUT4 protein and mRNA expression significantly decreased in the presence of OFA and LFA in a dose-dependent way. A significative enhancement of the NFkappaB mRNA expression and activity was verified at the presence of both fatty acids. However only an increase of the HIF-1a mRNA expression was observed by OFA and LFA.

Conclusion: The treatment with OFA and LFA reduce the SLC2A4 gene expression in L6 muscle cells. The present findings suggest that NFkappaB, but not HIF-1a, may be involved in this modulation.

Funding: FAPESP 07/56091-3.