Selective inhibition of synthesis of enzymes for de novo fatty acid biosynthesis by an endotoxin-induced mediator from exudate cells.
An endotoxin-induced mediator from exudate cells markedly suppresses the activities of the key enzymes for de novo fatty acid biosynthesis--acetyl-CoA carboxylase [acetyl-CoA:carbon dioxide ligase (ADP-forming), EC 6.4.1.2] and fatty acid synthetase--in differentiating 3T3-L1 murine preadipocytes. The loss in activity, at least in part, appears to be due to a specific effect on the synthesis of the enzymes, as determined by a decreased incorporation of [35S]methionine into immunoadsorbable acetyl-CoA carboxylase and fatty acid synthetase when the cells were exposed to the mediator. During this exposure, the radiolabeling of proteins with [35S]methionine in a particulate fraction was decreased by nearly 50% with little change in the soluble protein fraction. Sodium dodecyl sulfate/polyacrylamide gel analysis of the labeled protein indicated no major disturbances of protein synthesis in general; however, the syntheses of specific proteins in both the soluble and particulate fractions were enhanced or depressed. The present study demonstrates that endotoxin promotes the release of a mediator from exudate cells that regulates key anabolic activities in adipose cells.
D000103:Acetyl-CoA Carboxylase / Q000096:biosynthesis*; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D002460:Cell Line; D004731:Endotoxins / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000096:biosynthesis*; D008025:Ligases / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D014176:Protein Biosynthesis
D004731:Endotoxins; D064429:Fatty Acid Synthases; D008025:Ligases; D000103:Acetyl-CoA Carboxylase