PMID- 10585467
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 50
DP  - 1999 Dec 10
TI  - Sterol regulatory element-binding protein-1 as a key transcription factor for
      nutritional induction of lipogenic enzyme genes.
PG  - 35832-9
AB  - To elucidate the physiological role of sterol regulatory element-binding
      protein-1 (SREBP-1), the hepatic mRNA levels of genes encoding various lipogenic 
      enzymes were estimated in SREBP-1 gene knockout mice after a fasting-refeeding
      treatment, which is an established dietary manipulation for the induction of
      lipogenic enzymes. In the fasted state, the mRNA levels of all lipogenic enzymes 
      were consistently low in both wild-type and SREBP-1(-/-) mice. However, the
      absence of SREBP-1 severely impaired the marked induction of hepatic mRNAs of
      fatty acid synthetic genes, such as acetyl-CoA carboxylase, fatty acid synthase, 
      and stearoyl-CoA desaturase, that was observed upon refeeding in the wild-type
      mice. Furthermore, the refeeding responses of other lipogenic enzymes,
      glycerol-3-phosphate acyltransferase, ATP citrate lyase, malic enzyme,
      glucose-6-phosphate dehydrogenase, and S14 mRNAs, were completely abolished in
      SREBP-1(-/-) mice. In contrast, mRNA levels for cholesterol biosynthetic genes
      were elevated in the refed SREBP-1(-/-) livers accompanied by an increase in
      nuclear SREBP-2 protein. When fed a high carbohydrate diet for 14 days, the mRNA 
      levels for these lipogenic enzymes were also strikingly lower in SREBP-1(-/-)
      mice than those in wild-type mice. These data demonstrate that SREBP-1 plays a
      crucial role in the induction of lipogenesis but not cholesterol biosynthesis in 
      liver when excess energy by carbohydrates is consumed.
FAU - Shimano, H
AU  - Shimano H
AD  - Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo
      113-8655, Japan. shimano-tky@umin.ac.jp
FAU - Yahagi, N
AU  - Yahagi N
FAU - Amemiya-Kudo, M
AU  - Amemiya-Kudo M
FAU - Hasty, A H
AU  - Hasty AH
FAU - Osuga, J
AU  - Osuga J
FAU - Tamura, Y
AU  - Tamura Y
FAU - Shionoiri, F
AU  - Shionoiri F
FAU - Iizuka, Y
AU  - Iizuka Y
FAU - Ohashi, K
AU  - Ohashi K
FAU - Harada, K
AU  - Harada K
FAU - Gotoda, T
AU  - Gotoda T
FAU - Ishibashi, S
AU  - Ishibashi S
FAU - Yamada, N
AU  - Yamada N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Srebf1 protein, mouse)
RN  - 0 (Srebf2 protein, mouse)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 0 (Sterol Regulatory Element Binding Protein 2)
RN  - 0 (Transcription Factors)
RN  - 0 (Triglycerides)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
RN  - EC 1.14.19.1 (Stearoyl-CoA Desaturase)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
RN  - EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase)
RN  - EC 6.4.1.2 (Acetyl-CoA Carboxylase)
SB  - IM
MH  - Acetyl-CoA Carboxylase/biosynthesis/genetics
MH  - *Animal Nutritional Physiological Phenomena
MH  - Animals
MH  - *CCAAT-Enhancer-Binding Proteins
MH  - Cholesterol/blood/metabolism
MH  - DNA-Binding Proteins/deficiency/genetics/*metabolism
MH  - Diet
MH  - Eating
MH  - Enzyme Induction
MH  - Fasting
MH  - Fatty Acid Synthases/biosynthesis/genetics
MH  - Fatty Acids, Nonesterified/blood
MH  - Female
MH  - Gene Expression Regulation
MH  - *Gene Expression Regulation, Enzymologic
MH  - Hydroxymethylglutaryl CoA Reductases/biosynthesis/genetics
MH  - Hydroxymethylglutaryl-CoA Synthase/genetics
MH  - Liver/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Nuclear Proteins/deficiency/genetics/*metabolism
MH  - RNA, Messenger/genetics
MH  - Stearoyl-CoA Desaturase/biosynthesis/genetics
MH  - Sterol Regulatory Element Binding Protein 1
MH  - Sterol Regulatory Element Binding Protein 2
MH  - Transcription Factors/genetics/*metabolism
MH  - Triglycerides/blood/metabolism
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - 10.1074/jbc.274.50.35832 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 10;274(50):35832-9. doi: 10.1074/jbc.274.50.35832.