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

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 beta-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 mu M, 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 glucocorticold-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 (PGE(2) and PGF(2 alpha) at 10 mu M) 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.