Journal Article

Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice

Horton, J.D. (University of Texas Southwestern Medical Center, Dallas, TX.), Shimano, H, Bashmakov, Y, Shimomura, I

1998

Overview

Hepatic lipid synthesis is known to be regulated by food consumption. In rodents fasting decreases the synthesis of cholesterol as well as fatty acids. Refeeding a high carbohydrate/low fat diet enhances fatty acid synthesis by 5- to 20-fold above the fed state, whereas cholesterol synthesis returns only to the prefasted level. Sterol regulatory element binding proteins (SREBPs) are transcription factors that regulate genes involved in cholesterol and fatty acid synthesis. Here, we show that fasting markedly reduces the amounts of SREBP-1 and -2 in mouse liver nuclei, with corresponding decreases in the mRNAs for SREBP-activated target genes. Refeeding a high carbohydrate/low fat diet resulted in a 4- to 5-fold increase of nuclear SREBP-1 above nonfasted levels, whereas nuclear SREBP-2 protein returned only to the non-fasted level. The hepatic mRNAs for fatty acid biosynthetic enzymes increased 5- to 10-fold above nonfasted levels, a pattern that paralleled the changes in nuclear SREBP-1. The hepatic mRNAs for enzymes involved in cholesterol synthesis returned to the nonfasted level, closely following the pattern of nuclear SREBP-2 regulation. Transgenic mice that overproduce nuclear SREBP-1c failed to show the normal decrease in hepatic mRNA levels for cholesterol and fatty acid synthetic enzymes upon fasting. We conclude that SREBPs are regulated by food consumption in the mouse liver and that the decline in nuclear SREBP-1c upon fasting may explain in part the decrease in mRNAs encoding enzymes of the fatty acid biosynthetic pathway

• Publisher: National Academy of Sciences of the United States of America,National Acad Sciences,National Academy of Sciences,The National Academy of Sciences
• Subject: ALIMENTACION / ALIMENTATION / analysis / ANIMAL TRANSGENIQUE / ANIMALES TRANSGENICOS / Animals / ARN MENSAJERO / ARN MESSAGER / Biochemistry / Biological Sciences / biosynthesis / BLOOD LIPIDS / CCAAT-Enhancer-Binding Proteins / CHOLESTEROL / Cholesterol - biosynthesis / cholesterol metabolism / Cholesterols / COLESTEROL / DIET / DIETA / DNA-Binding Proteins / DNA-Binding Proteins - genetics / DNA-Binding Proteins - metabolism / Eating / ENZIMAS / ENZYME / ENZYMES / EXPRESION GENICA / EXPRESSION DES GENES / FACTEUR DE TRANSCRIPTION / FACTORES DE TRANSCRIPCION / Fasting / Fatty Acids / Fatty Acids - biosynthesis / FEEDING / FOIE / GENE EXPRESSION / Gene Expression Regulation / GENERO HUMANO / Genes / GENETIC REGULATION / GENETICA / GENETICS / GENETIQUE / GENRE HUMAIN / HEMOLIPIDOS / HIGADO / HIGH CARBOHYDRATE LOW FAT DIET / humans / INANICION / INANITION / LIPIDE SANGUIN / LIPOGENESE / LIPOGENESIS / LIVER / Liver - metabolism / Male / MANKIND / MESSENGER RNA / METABOLISM / METABOLISME / METABOLISMO / MICE / Mice, Transgenic / Nuclear membrane / Nuclear Proteins / Nuclear Proteins - genetics / Nuclear Proteins - metabolism / promoter regions / PROMOTERS / Proteins / RATON / REFEEDING / REGIME ALIMENTAIRE / repletion / RNA, Messenger / RNA, Messenger - analysis / RNA, Messenger - genetics / Rodents / SOURIS / STARVATION / Sterol Regulatory Element Binding Protein 1 / TRANSCRIPCION / TRANSCRIPTION / transcription (genetics) / TRANSCRIPTION FACTORS / Transcription Factors - genetics / Transcription Factors - metabolism / TRANSGENIC ANIMALS / triacylglycerols / TRIGLICERIDOS / TRIGLYCERIDE / TRIGLYCERIDES