Jd. Horton et al., REGULATION OF STEROL REGULATORY ELEMENT-BINDING PROTEINS IN LIVERS OFFASTED AND REFED MICE, Proceedings of the National Academy of Sciences of the United Statesof America, 95(11), 1998, pp. 5987-5992
Hepatic lipid synthesis is known to be regulated by food consumption.
In rodents fasting decreases the synthesis of cholesterol as well as f
atty acids. Refeeding a high carbohydrate/low fat diet enhances fatty
acid synthesis by 5- to 20-fold above the fed state, whereas cholester
ol synthesis returns only to the prefasted level. Sterol regulatory el
ement binding proteins (SREBPs) are transcription factors that regulat
e genes involved in cholesterol and fatty acid synthesis. Here, we sho
w that fasting markedly reduces the amounts of SREBP-1 and -2 in mouse
liver nuclei, with corresponding decreases in the mRNAs for SREBP-act
ivated target genes. Refeeding a high carbohydrate/low fat diet result
ed in a 4- to 5-fold increase of nuclear SREBP-1 above nonfasted level
s, whereas nuclear SREBP-2 protein returned only to the nonfasted leve
l, The hepatic mRNAs for fatty acid biosynthetic enzymes increased 5-
to 10-fold above nonfasted levels, a pattern that paralleled the chang
es in nuclear SREBP-1. The hepatic mRNAs for enzymes involved in chole
sterol synthesis returned to the nonfasted level, closely following th
e pattern of nuclear SREBP-2 regulation. Transgenic mice that overprod
uce nuclear SREBP-1c failed to show the normal decrease in hepatic mRN
A levels for cholesterol and fatty acid synthetic enzymes upon fasting
, We conclude that SREBPs are regulated by food consumption in the mou
se liver and that the decline in nuclear SREBP-1c upon fasting may exp
lain in part the decrease in mRNAs encoding enzymes of the fatty acid
biosynthetic pathway.