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Oleic and linoleic unsaturated fatty acids repressing Slc2a4 gene via NF-kB and SREBP-1.

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Author(s):
Ana Claudia Poletto
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Ubiratan Fabres Machado; Karla Fabiana Santana de Melo Cabral Fagundes; Daniela Tomie Furuya; Daniel Giannella Neto; Marisa Passarelli
Advisor: Ubiratan Fabres Machado
Abstract

High elevated levels of some free fatty acids (FFAs) are associated with insulin resistance in skeletal muscle. The mechanisms by which FFAs impair this hormone sensitivity need to be clarified; nevertheless, its effects in the modulation of NF-kB, SREBP-1c, HIF-1<font face=\"Symbol\">&#945;, LXR<font face=\"Symbol\">&#945; and PPARg which are related with Slc2a4 gene regulation have been suggested. The goal of this study was to investigate the action of oleic (OFA) and linoleic (LFA) fatty acids, in L6 muscle cells, in Slc2a4 regulation. The GLUT4 protein and mRNA expression decreased in the presence of OFA and LFA. The reduced GLUT4 expression was related to a significative enhancement of the NFkappaB mRNA expression and binding activity in presence of both FFAs and a decrease of SREBP-1 mRNA and binding activity in the Slc2a4. OFA and LFA increase LXR<font face=\"Symbol\">&#945;, PPARg and HIF-1<font face=\"Symbol\">&#945; mRNA expression, but only a reduction in PPARg binding activity was verified in presence of the LFA. A reduction in GLUT4 expression in the presence of OFA and LFA was detected and related with NF-kB and SREBP-1 binding activity in the Slc2a4 gene. (AU)