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, Arachidoni c acid (20:4, n-6) and eicosapentaenoic acid (20:5, n-3) suppressed mR NAs encoding fatty acid synthase (FAS) and S14, but had no effect on b eta-actin, Using a clonal adipocyte cell line containing a stably inte grated S14CAT fusion gene, oleic acid (18:1, n-9), arachidonic acid (2 0:4, n-6) and eicosapentaenoic acid (20:5, n-3) inhibited chlorampheni col 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 suppres sed basal CAT activity, but did not affect glucocorticold-mediated ind uction of S14CAT expression. The effect of 20:4, n-6 on S14CAT express ion was blocked by an inhibitor of cyclooxygenase implicating involvem ent 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 inhibi ts lipogenic gene expression in 3T3-L1 adipocytes through a prostanoid pathway. This mechanism of control differs from the polyunsaturated f atty acid-mediated suppression of hepatic lipogenic gene expression.