12421847

pubmed:Citation

11

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.

eng

IM

MEDLINE

0022-3166

Print

NLM

3333-9

pubmed-meshheading:12421847-Animals, pubmed-meshheading:12421847-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:12421847-Cell Nucleus, pubmed-meshheading:12421847-DNA-Binding Proteins, pubmed-meshheading:12421847-Dietary Fats, Unsaturated, pubmed-meshheading:12421847-Fatty Acid Synthetase Complex, pubmed-meshheading:12421847-Fish Oils, pubmed-meshheading:12421847-Gene Expression Regulation, pubmed-meshheading:12421847-Hydroxymethylglutaryl-CoA Synthase, pubmed-meshheading:12421847-Kinetics, pubmed-meshheading:12421847-Liver, pubmed-meshheading:12421847-Male, pubmed-meshheading:12421847-Protein Precursors, pubmed-meshheading:12421847-RNA, Messenger, pubmed-meshheading:12421847-Rats, pubmed-meshheading:12421847-Rats, Sprague-Dawley, pubmed-meshheading:12421847-Safflower Oil, pubmed-meshheading:12421847-Sterol Regulatory Element Binding Protein 1, pubmed-meshheading:12421847-Sterol Regulatory Element Binding Protein 2, pubmed-meshheading:12421847-Transcription Factors

Dietary polyunsaturated fats regulate rat liver sterol regulatory element binding proteins-1 and -2 in three distinct stages and by different mechanisms.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't