Arachidonic acid metabolites of the lipoxygenase as well as the cyclooxygenase pathway may be involved in regulating preadipocyte differentiation.

Abstract

Conditions that trigger preadipocyte differentiation in vivo have yet to be elucidated. To investigate the role of endogenous arachidonic acid (AA) metabolites on adipose tissue growth, rat preadipocytes in primary culture were induced to differentiate using medium conditioned by isolated mature adipocytes (ACM). Differentiation was determined by assay of glycerol-3-phosphate dehydrogenase (GPDH). When collected in the presence of indomethacin (10 nmol/L) to inhibit prostaglandin (PG) synthesis by adipocytes, ACM induced greater differentiation (GPDH activity, 405 +/- 68 nmol NADH used/min/mg protein) than when indomethacin was added postcollection to inhibit preadipocyte PG synthesis (205 +/- 24, P < .05) or ACM alone (304 +/- 55). This suggested that PGs released by adipocytes inhibited differentiation, whereas those released by preadipocytes appeared to act in an autocrine manner to stimulate differentiation. However, 24-hour collections of ACM contained 125 pmol/L PGE2 and 900 pmol/L PGI2, concentrations too low to promote differentiation when added exogenously. Nordihydroguaiaretic acid (NDGA; 10 pmol/L), an inhibitor of lipoxygenase (LOX), stimulated the ACM-induced increase in GPDH activity (ACM, 99 +/- 13; ACM + NDGA, 369 +/- 130). In contrast, when differentiation was induced by a hormonal cocktail (MIX), including insulin and corticosterone, NDGA decreased GPDH activity (MIX, 329 +/- 66; MIX + NDGA, 142 +/- 40; P < .03). We concluded that preadipocyte differentiation within adipose tissue may be subject to both positive and negative regulators derived from AA metabolism resulting from both LOX and cyclooxygenase (COX) activity.