出版社：American Society for Biochemistry and Molecular Biology
摘要：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 20% of control at 60–250 µM 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 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.
Abbreviations: AA, arachidonic acid; BADGE, bisphenol A diglycidyl ether; C/EBP, CCAAT/enhancer binding protein; COX, cyclooxygenase; DHA, docosahexaenoic acid; EP, E-prostanoid; EPA, eicosapentaenoic acid; FP, F-prostanoid; LA, linoleic acid; LDH, lactate dehydrogenase; LN, -linolenic acid; LUC, luciferase; LXR, liver X receptor; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; OA, oleic acid; PA, palmitic acid; PG, prostaglandin; PI3K, phosphatidylinositol 3-kinase; PPAR, peroxisome proliferator-activated receptor; RELM, resistin-like molecule; RXR, retinoic acid X receptor; SA, stearic acid; SREBP, sterol-regulatory element binding protein; TTA, tetradecylthioacetic acid
