Control of life cycle of mouse adipogenic 3T3-L1 cells by dietary lipids and metabolic factors.
Adipocytes function not only as in the storage and mobilization of lipids but also as endocrine cells by secreting tumor necrosis factor-alpha (TNF-alpha), free fatty acids, and other cytokines. To study the effects of dietary lipids and metabolic factors on the control of the life cycle of adipocytes, we utilized mouse 3T3-L1 preadipocytes that could be induced to differentiate into adipocytes. To evaluate the role of endogenous prostaglandins (PGs) in the adipogenic changes, we examined the effect of specific inhibitors of cyclooxygenase (COX). SC-560, a specific COX-1 inhibitor, suppressed adipogenesis dose dependently, suggesting a role of constitutive COX-1 in the endogenous synthesis of PGs, including PGJ2 derivatives formed by mature adipocytes with the ability to promote adipogenesis. NS-398, a COX-2 inhibitor, had little influence on the maturation processes. Both COX inhibitors were effective in stimulating apoptosis of preadipocytes induced by TNF-alpha, indicating that both PGE2 and PGF2alpha produced by preadipocytes through the action of both COX isoforms serve as survival factors. However, the effect of both inhibitors was negligible for the proliferation of preadipocytes. Moreover, conjugated linolenic acid from bitter gourd at lower concentrations that was without effects by itself synergistically stimulated TNF-alpha-induced apoptosis. Therefore, dietary lipid factors are capable of controlling the life cycle of adipocytes together with metabolic factors.