Original Article

Arachidonic acid inhibits lipogenic gene expression in 3T3-L1 adipocytes through a prostanoid pathway

Correspondence to: Donald B. Jump.

This report examines the effect of polyunsaturated fatty acids (PUFA) on lipogenic gene expression in cultured 3T3-L1 adipocytes. Arachidonic acid (20:4, n–6) and eicosapentaenoic acid (20:5, n–3) suppressed mRNAs encoding fatty acid synthase (FAS) and S14, but had no effect on ß-actin. Using a clonal adipocyte cell line containing a stably integrated S14CAT fusion gene, oleic acid (18:1, n–9), arachidonic acid (20:4, n–6) and eicosapentaenoic acid (20:5, n–3) inhibited chloramphenicol acetyltransferase (CAT) activity with an ED₅₀ of 800, 50, and 400 µM, respectively. Given the high potency of 20:4, n–6, its effect on adipocyte gene expression was characterized. Arachidonic acid suppressed basal CAT activity, but did not affect glucocorticoid-mediated induction of S14CAT expression. The effect of 20:4, n–6 on S14CAT expression was blocked by an inhibitor of cyclooxygenase implicating involvement of prostanoids. Prostaglandins (PGE₂ and PGF₂ at 10 µM) inhibited CAT activity through a pertussis toxin-sensitive G_i/G_o-coupled signalling cascade.

Our results suggest that 20:4, n–6 inhibits lipogenic gene expression in 3T3-L1 adipocytes through a prostanoid pathway. This mechanism of control differs from the polyunsaturated fatty acid-mediated suppression of hepatic lipogenic gene expression.—Mater, M. K., D. Pan, W. G. Bergen, and D. B. Jump. Arachidonic acid inhibits lipogenic gene expression in 3T3-L1 adipocytes through a prostanoid pathway. J. Lipid Res. 1998. 39: 1327–1334.

Supplementary key words: adipocytes, polyunsaturated fatty acids, arachidonic acid, transcription, PGE₂, inositol phosphate/calcium, prostanoids

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