Control of life cycle of mouse adipogenic 3T3-L1 cells by dietary lipids and metabolic factors |
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Authors: | Kohji Nishimura Yoko Hatano Tsutomu Setoyama Hirohumi Tsumagari Kazuo Miyashita Shan Lu Mitsuo Jisaka Tsutomu Nagaya Kazushige Yokota |
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Institution: | (1) Department of Life Science and Biotechnology, Shimane University, Matsue, 690-8504 Shimane, Japan;(2) Division of Marine Bioscience, Graduate School of Fisheries Science, Hokkaido University, 041-8611 Hakodate, Japan |
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Abstract: | Adipocytes function not only as in the storage and mobilization of lipids but also as endocrine cells by secreting tumor necrosis
factor-α (TNF-α), 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-α,
indicating that both PGE2 and PGF2α 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-α-induced apoptosis. Therefore, dietary
lipid factors are capable of controlling the life cycle of adipocytes together with metabolic factors. |
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Keywords: | Adipocyte apoptosis arachidonate cascade conjugated linolenic acid cyclooxygenase lipoxygenase obesity peroxisome proliferator-activated receptor γ |
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