Dietary Polyunsaturated Fats Regulate Rat Liver Sterol Regulatory Element Binding Proteins-1 and -2 in Three Distinct Stages and by Different Mechanisms

• Published in: The Journal of nutrition Vol. 132; no. 11; pp. 3333 - 3339
• Main Authors: Xu, Jing, Cho, Hyekung, O'Malley, Sean, Clarke, Steven D., Park, Jung H.Y.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.11.2002; American Society for Nutritional Sciences; American Institute of Nutrition
• Subjects: Animals; Biological and medical sciences; CCAAT-Enhancer-Binding Proteins - genetics; CCAAT-Enhancer-Binding Proteins - metabolism; Cell Nucleus - metabolism; Diet; Dietary Fats, Unsaturated - pharmacology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fatty Acid Synthases - genetics; Fatty acids; Fish Oils - administration & dosage; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Hydroxymethylglutaryl-CoA Synthase - genetics; Kinetics; Liver; Liver - metabolism; Liver - ultrastructure; Liver. Bile. Biliary tracts; Male; polyunsaturated fatty acids; Protein Precursors - metabolism; Proteins; Rats; Rats, Sprague-Dawley; RNA, Messenger - analysis; Rodents; Safflower Oil - administration & dosage; sterol regulatory element binding protein; Sterol Regulatory Element Binding Protein 1; Sterol Regulatory Element Binding Protein 2; transcription; Transcription Factors - genetics; Transcription Factors - metabolism; Vertebrates: digestive system; sterol regulatory element binding protein; HMG; SREBP; transcription; liver; PUFA; polyunsaturated fatty acids; FAS; rats; GAPDH; Rat; Transcription; Digestive system; Liver; Rodentia; Polyunsaturated fatty acid; Lipids; Feeding; Binding protein; Vertebrata; Mammalia; Diet; Animal; Regulatory sequence; Macronutrient; Sterol
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/132.11.3333

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.