Intracellular fatty acid downregulates ob gene expression in 3T3-L1 adipocytes.
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.
Arai
Takeo
T
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. takeo.arai@gsk.com
Kawakami
Yasushi
Y
Matsushima
Teruhiko
T
Okuda
Yukichi
Y
Yamashita
Kamejiro
K
D016475:3T3 Cells; D017667:Adipocytes / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002855:Chromatography, Thin Layer; D002914:Chylomicrons / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D015870:Gene Expression; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007700:Kinetics; D020738:Leptin / Q000235:genetics*; D050356:Lipid Metabolism; D051379:Mice; D010168:Palmitates / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D014226:Triazenes / Q000494:pharmacology
D002914:Chylomicrons; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D020738:Leptin; D010168:Palmitates; D014226:Triazenes; C022776:2-bromopalmitate; D019308:Palmitic Acid; D012313:RNA; C034613:triacsin C