Resistin expression in 3T3-L1 adipocytes is reduced by arachidonic acid.
The resistin gene is expressed in adipocytes and encodes a protein proposed to link obesity and type 2 diabetes. Increased plasma 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 approximately 20% of control at 60-250 muM concentration. Selective inhibitors of cyclooxygenase-1 and of mitogen-activated protein kinase kinase counteracted AA-induced reduction in resistin mRNA levels. Transient overexpression of sterol-regulatory element binding protein-1a (SREBP-1a) activated the resistin promoter, but there was no reduction in the abundance of approximately 65 kDa mature SREBP-1 after AA exposure. Actinomycin D as well as cycloheximide abolished the AA-induced reduction of resistin mRNA levels, indicating dependence on de novo transcription and translation. Our data 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 the beneficial effect of ingesting PUFAs on insulin sensitivity.
Haugen
Fred
F
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Zahid
Naeem
N
Dalen
Knut T
KT
Hollung
Kristin
K
Nebb
Hilde I
HI
Drevon
Christian A
CA
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology; D051545:Cyclooxygenase 1; D004268:DNA-Binding Proteins / Q000502:physiology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006729:Hormones, Ectopic / Q000235:genetics*; D008565:Membrane Proteins; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis; D052243:Resistin; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D006729:Hormones, Ectopic; D008565:Membrane Proteins; D012333:RNA, Messenger; D052243:Resistin; C499623:Retn protein, mouse; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases