Polyunsaturated fatty acid inhibition of fatty acid synthase transcription is independent of PPAR activation.
Polyunsaturated fatty acids (PUFA) of the (n-6) and (n-3) families inhibit the rate of gene transcription for a number of hepatic lipogenic and glycolytic genes, e.g., fatty acid synthase (FAS). In contrast, saturated and monounsaturated fatty acids have no inhibitory capability. The suppression of gene transcription resulting from the addition of PUFA to a high carbohydrate diet: occurs quickly (< 3 h) after its addition to a high glucose diet; can be recreated with hepatocytes cultured in a serum-free medium containing insulin and glucocorticoids; can be demonstrated in diabetic rats fed fructose; and is independent of glucagon. While the nature of the intracellular PUFA inhibitor is unclear, it appears that delta-6 desaturation is a required step in the process. Recently, the fatty acid activated nuclear factor, peroxisome-proliferator activated receptor (PPAR) was suggested to be the PUFA-response factor. However, the potent PPAR activators ETYA and Wy-14643 did not suppress hepatic expression of FAS, but did induce the PPAR-responsive gene, acyl-CoA oxidase (AOX). Similarly, treating rat hepatocytes with 20:4 (n-6) suppressed FAS expression but had no effect on AOX. Thus, it appears that the PUFA regulation of gene transcription involves a PUFA-response factor that is independent from PPAR.
Clarke
S D
SD
Department of Human Ecology, University of Texas at Austin 78712, USA.
Turini
M
M
Jump
D B
DB
Abraham
S
S
Reedy
M
M
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003314:Corn Oil; D003369:Cottonseed Oil; D004041:Dietary Fats / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000096:biosynthesis*; D005395:Fish Oils; D005527:Food, Fortified; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
D003369:Cottonseed Oil; D004041:Dietary Fats; D005395:Fish Oils; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D015117:5,8,11,14-Eicosatetraynoic Acid; C033266:Menhaden oil; D009637:Masoprocol; D003314:Corn Oil; D064429:Fatty Acid Synthases