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

Abstract

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 β-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 PGF2α at 10 μm) inhibited CAT activity through a pertussis toxin-sensitive Gi/Go-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.

Keywords

• adipocytes
• polyunsaturated fatty acids
• arachidonic acid
• transcription
• PGE2
• inositol phosphate/calcium