CoChat
Sign Up
Cited by 577

The DOI matches its Crossref record.

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

Horton, Jay D., Bashmakov, Yuriy, Shimomura, Iichiro, Shimano, Hitoshi·1998·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.95.11.5987
Open this paper in CoChat — free account

Abstract

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 nonfasted 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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.95.11.5987

Cites

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Hepatic SREBP2 activity and cholesterol biosynthesis rate fall while fasting and rise greatly upon refeeding.

    “Substantial evidence supports the conclusion that hepatic SREBP2 activity and cholesterol biosynthesis rate fall while fasting and rise greatly upon refeeding, indicating the existence of feeding-responsive signaling pathways upregulating hepatic cholesterol synthesis in the presence of dietary nutrition (Horton et al., 1998; Liang et al., 2002; Matsuda et al., 2001; Slakey et al., 1972).”

    From GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis (2019) · cites this paper as Horton et al., 1998

    The Results and Discussion report that hepatic nuclear SREBP-2 falls during fasting and recovers upon refeeding. But they specify that it returns only to the nonfasted level; the Abstract says cholesterol synthesis likewise returns only to its prefasted level. The paper therefore supports a fasting decline and refeeding recovery, but not an increase greatly beyond baseline. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Hepatic SREBP2 activity and expression of its target genes such as HMGCR and LDLR fall while fasting and rise substantially upon refeeding.

    “Abundant evidence demonstrates that hepatic SREBP2 activity and expression of its target genes such as HMGCR and LDLR fall while fasting and rise substantially upon refeeding”

    From GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis (2019) · cites this paper as Horton et al., 1998

  • There exist feeding-responsive signaling pathways that upregulate hepatic cholesterol synthesis in the presence of dietary nutrition.

    “Substantial evidence supports the conclusion that hepatic SREBP2 activity and cholesterol biosynthesis rate fall while fasting and rise greatly upon refeeding, indicating the existence of feeding-responsive signaling pathways upregulating hepatic cholesterol synthesis in the presence of dietary nutrition (Horton et al., 1998; Liang et al., 2002; Matsuda et al., 2001; Slakey et al., 1972).”

    From GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis (2019) · cites this paper as Horton et al., 1998

  • During fasting, SREBP-dependent lipid/cholesterol synthesis is rapidly diminished in the mouse liver.

    “During fasting, SREBP-dependent lipid/cholesterol synthesis is rapidly diminished in the mouse liver; however, the mechanism has remained incompletely understood.”

    From Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP (2010) · cites this paper as Horton et al. 1998

  • The mature nuclear forms of SREBP-1 and SREBP-2 are abundant in the mouse liver during feeding, and during fasting SREBPs are markedly down-regulated, correlating with decreased lipogenic and cholesterogenic gene expression.

    “The mature nuclear forms of SREBP-1 and SREBP-2 are abundant in the mouse liver during feeding, and the expression of fatty acid and cholesterol biosynthesis genes is high, whereas, during fasting, SREBPs are markedly down-regulated, correlating with decreased lipogenic and cholesterogenic gene expression (Horton et al. 1998).”

    From Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP (2010) · cites this paper as Horton et al. 1998

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 27

  1. 10.1016/S0092-8674(00)80213-5 · DOI · Paper page
  2. 10.1016/S0092-8674(05)80095-9 · DOI
  3. 10.1128/mcb.13.8.4753-4759.1993 · DOI
  4. 10.1073/pnas.90.24.11603 · DOI · Paper page
  5. 10.1074/jbc.271.21.12247 · DOI
  6. 10.1073/pnas.93.2.945 · DOI
  7. 10.1074/jbc.272.15.10295 · DOI
  8. 10.1074/jbc.271.43.26461 · DOI
  9. 10.1016/S0022-2275(20)37181-9 · DOI
  10. 10.1074/jbc.271.51.32689 · DOI
  11. 10.1172/JCI118951 · DOI
  12. 10.1074/jbc.272.11.7298 · DOI
  13. 10.1073/pnas.94.23.12354 · DOI · Paper page
  14. 10.1073/pnas.92.4.935 · DOI · Paper page
  15. 10.1172/JCI119247 · DOI
  16. 10.1172/JCI119248 · DOI · Paper page
  17. 10.1152/physrev.1995.75.1.47 · DOI
  18. 10.1016/S0021-9258(19)52391-2 · DOI
  19. 10.1172/JCI1411 · DOI
  20. 10.1093/nar/12.8.3563 · DOI
  21. 10.1172/JCI119746 · DOI · Paper page
  22. 10.1016/0888-7543(95)80009-B · DOI
  23. 10.1074/jbc.270.40.23235 · DOI
  24. 10.1111/j.1432-1033.1992.tb16797.x · DOI
  25. 10.1074/jbc.272.42.26367 · DOI
  26. 10.1016/S0021-9258(19)85265-1 · DOI · Paper page
  27. 10.1016/S0021-9258(19)85266-3 · DOI · Paper page

Cited by

Sorted by citations

Metadata

Authors
Horton, J. D., Bashmakov, Y., Shimomura, I., & Shimano, H.
Affiliations
Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Room L5-238, Dallas, TX 75235-9046
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1998-05-26
Volume
95
Issue
11
Pages
5987-5992
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.95.11.5987
Cited by
577
References
0
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review