Arai Takeo, Kawakami Yasushi, Matsushima Teruhiko, Okuda Yukichi, Yamashita Kamejiro
Division of Endocrinology and Metabolism, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-city, 305, Ibaraki, Japan.
Biochem Biophys Res Commun. 2002 Oct 11;297(5):1291-6. doi: 10.1016/s0006-291x(02)02376-8.
The effect of intracellular free fatty acid (FFA) accumulation on ob gene expression in adipocytes was examined. In fully differentiated 3T3-L1 adipocytes, triacsin C, a specific acyl CoA synthetase inhibitor with a K(i) of 8.97 microM, inhibited ob gene expression by 20% at 5 x 10(-5)M. At this concentration, triacsin C induced accumulation of intracellular FFA. Treatment with both chylomicron and triacsin C reduced ob gene expression more than treatment with triacsin C alone. Treatment with 2-bromopalmitate, a poorly metabolizable palmitate analog, reduced ob gene expression by 50% at 10(-4)M, but palmitate at the same concentration had no effect. This is the first demonstration that the ob gene is downregulated by intracellular FFA accumulation, thereby raising the possibility that ob product is regulated in response to lipolysis.
研究了细胞内游离脂肪酸（FFA）积累对脂肪细胞中ob基因表达的影响。在完全分化的3T3-L1脂肪细胞中，三辛菌素C（一种特异性酰基辅酶A合成酶抑制剂，K(i)为8.97 microM）在5×10(-5)M时可使ob基因表达抑制20%。在此浓度下，三辛菌素C诱导细胞内FFA积累。与乳糜微粒和三辛菌素C联合处理相比，单独用三辛菌素C处理对ob基因表达的降低作用更大。用2-溴棕榈酸酯（一种代谢性较差的棕榈酸类似物）处理，在10(-4)M时可使ob基因表达降低50%，但相同浓度的棕榈酸则无作用。这首次证明ob基因可被细胞内FFA积累下调，从而增加了ob产物受脂解作用调节的可能性。
