Arachidonic acid inhibition of insulin action and phosphoinositide turnover in fat cells

Abstract

Incubation of isolated rat adipocytes with 1 μM arachidonic acid (20:4) coupled to equimolar amounts of bovine serum albumin (BSA) results in the cellular uptake of the fatty acid and a subsequent inhibition of insulin-stimulated antilipolysis and lipogenesis without altering glucose transport. These effects are apparently not mediated at the insulin receptor level since insulin binding is not altered in arachidonate-enriched fat cells. In addition, effects on antilipolytic and lipogenic are not specific for arachidonic acid. Oleic or palmitic acid can mimic these effects in both insulin-stimulated and PGE 2-stimulated cells. Adipocyte enrichment with 20:4, however, specifically inhibits the insulin-stimulated turnover of phosphoinositides. The latter can be specifically prevented by preincubation with ibuprofen. These results suggest that the level of intracellular arachidonate may play a major role in modulating insulin-stimulated phosphoinositide turnover and thereby indirectly regulate certain aspects of insulin action which involve lipid metabolism.