Submitted on September 14, 2004
Revised on September 29, 2004
Accepted on October 1, 2004
Resistin expression in 3T3-L1 adipocytes is reduced by arachidonic acid
Fred Haugen, Naeem Zahid, Knut T. Dalen, Kristin Hollung, Hilde I. Nebb, and Christian A. Drevon
Department of Nutrition, University of Oslo, Oslo, Blindern N-0316
Corresponding Author: c.a.drevon{at}basalmed.uio.no
The resistin gene is expressed in adipocytes and encodes a protein proposed to link obesity and type 2 diabetes. Elevated plasma free fatty acid (FFA) is associated with insulin resistance. We examined the effect of separate FFAs on the expression of resistin mRNA in cultured murine 3T3-L1 adipocytes. The FFAs tested did not increase resistin expression, whereas both arachidonic acid (AA) and eicosapentaenoic acid (EPA) reduced resistin mRNA levels. AA was by far the most potent FFA, reducing resistin mRNA levels to ~ 20 % of control at 60-250 µM concentration. Selective inhibitors of cyclooxygenase (COX)-1, and of mitogen-activated protein kinase (MAPK) kinase (MEK), counteracted AA-induced reduction in resistin mRNA levels. Transient over-expression of sterol regulatory element-binding protein (SREBP)-1a activated the resistin promoter, but there was no reduction in the abundance of ~ 65 kDa mature SREBP-1 after AA-exposure. Actinomycin D as well as cycloheximide abolished AA-induced reduction of resistin mRNA levels, indicating dependence on de novo transcription and translation. Our data may suggest that reductions in resistin mRNA levels involve a destabilization of the resistin mRNA molecule. An inhibitory effect of AA and EPA on resistin expression may explain a beneficial effect of ingesting polyunsaturated fatty acids (PUFA) on insulin sensitivity.
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