Dietary polyunsaturated fats regulate rat liver sterol regulatory element binding proteins-1 and -2 in three distinct stages and by different mechanisms.
Male Sprague-Dawley rats, trained to consume their daily energy needs in a single 3-h meal (0900-1200 h), were used to examine the hypothesis that polyunsaturated fatty acids (PUFA) lowered the nuclear content of sterol regulatory element binding protein (SREBP)-1 and/or -2 by suppressing the proteolytic release of mature SREBP from the membrane-anchored precursor pool. The nuclear concentrations of hepatic SREBP-1 and -2 were 50 and 42% lower (P < 0.05) in rats that consumed a single PUFA-supplemented meal (i.e., 10 g fish oil/100 g fat-free diet) than in rats fed the fat-free diet alone. This was paralleled by 63 and 52% reductions in the expression of the SREBP-1 and -2 target genes, fatty acid synthase and HMG-CoA synthase, respectively; but the marked increase in the amount of precursor SREBP-1 and -2 resulting from meal ingestion was unaffected. After the consumption of a second meal of fish oil, the nuclear level of mature SREBP-1 was only 16% of that in rats fed the fat-free diet, but the amount of nuclear SREBP-2 was not different from the level in rats fed the fat-free diet. Again, the sizes of the SREBP-1 and -2 precursor pools were not reduced. A decrease in the hepatic concentration of precursor SREBP-1 did not occur until rats had consumed 5 meals of fish oil. At this point, the nuclear content of SREBP-2 was actually twofold higher (P < 0.05) in rats fed fish oil or safflower oil, but the amount of precursor SREBP-2 was unaffected. These data indicate that PUFA suppress the in vivo proteolytic release of SREBP-1 and -2, but the effect on SREBP-2 is transitory, possibly reflecting the ability of PUFA to enhance cholesterol losses via bile acid synthesis.
Xu
Jing
J
The Division of Nutritional Sciences and the Institute for Cellular and Molecular Biology, The University of Texas, Austin, TX 78712, USA.
Cho
Hyekung
H
O'Malley
Sean
S
Park
Jung H Y
JH
Clarke
Steven D
SD
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000235:genetics; D005395:Fish Oils / Q000008:administration & dosage; D005786:Gene Expression Regulation; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics; D007700:Kinetics; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012450:Safflower Oil / Q000008:administration & dosage; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D004042:Dietary Fats, Unsaturated; D005395:Fish Oils; D011498:Protein Precursors; D012333:RNA, Messenger; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D012450:Safflower Oil; D064429:Fatty Acid Synthases; D006904:Hydroxymethylglutaryl-CoA Synthase