A biotin analog inhibits acetyl-CoA carboxylase activity and adipogenesis.
Acetyl-CoA carboxylase catalyzes the first committed step in the synthesis of long chain fatty acids. In this study, we observed that treatment of 3T3-L1 cells with biotin chloroacetylated at the 1' nitrogen reduced the enzymatic activity of cytosolic acetyl-CoA carboxylase and concomitantly inhibited the differentiation of 3T3-L1 cells in a dose-dependent manner. Treatment with chloroacetylated biotin blocked the induction of PPARgamma, STAT1, and STAT5A expression that normally occurs with adipogenesis. Moreover, addition of chloroacetylated biotin inhibited lipid accumulation, as judged by Oil Red O staining. Our results support recent studies that indicate that acetyl-CoA carboxylase may be a suitable target for an anti-obesity therapeutic.
Levert
Keith L
KL
Division of Biochemistry and Molecular Biology, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Waldrop
Grover L
GL
Stephens
Jacqueline M
JM
D016475:3T3 Cells; D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects*; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D001710:Biotin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D050356:Lipid Metabolism; D051379:Mice; D008894:Milk Proteins; D008956:Models, Chemical; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D001391:Azo Compounds; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D008894:Milk Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; C494080:Stat1 protein, mouse; C494093:Stat5a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D001710:Biotin; D000103:Acetyl-CoA Carboxylase; C011049:oil red O