The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Polyunsaturated fatty acids suppress glycolytic and lipogenic genes through the inhibition of ChREBP nuclear protein translocation
Open accessAbstract
Dietary polyunsaturated fatty acids (PUFAs) are potent inhibitors of hepatic glycolysis and lipogenesis. Recently, carbohydrate-responsive element-binding protein (ChREBP) was implicated in the regulation by glucose of glycolytic and lipogenic genes, including those encoding L-pyruvate kinase (L-PK) and fatty acid synthase (FAS). The aim of our study was to assess the role of ChREBP in the control of L-PK and FAS gene expression by PUFAs. We demonstrated in mice, both in vivo and in vitro, that PUFAs [linoleate (C18:2), eicosapentanoic acid (C20:5), and docosahexaenoic acid (C22:6)] suppressed ChREBP activity by increasing ChREBP mRNA decay and by altering ChREBP translocation from the cytosol to the nucleus, independently of an activation of the AMP-activated protein kinase, previously shown to regulate ChREBP activity. In contrast, saturated [stearate (C18)] and monounsaturated fatty acids [oleate (C18:1)] had no effect. Since glucose metabolism via the pentose phosphate pathway is determinant for ChREBP nuclear translocation, the decrease in xylulose 5-phosphate concentrations caused by a PUFA diet favors a PUFA-mediated inhibition of ChREBP translocation. In addition, overexpression of a constitutive nuclear ChREBP isoform in cultured hepatocytes significantly reduced the PUFA inhibition of both L-PK and FAS gene expression. Our results demonstrate that the suppressive effect of PUFAs on these genes is primarily caused by an alteration of ChREBP nuclear translocation. In conclusion, we describe a novel mechanism to explain the inhibitory effect of PUFAs on the genes encoding L-PK and FAS and demonstrate that ChREBP is a pivotal transcription factor responsible for coordinating the PUFA suppression of glycolytic and lipogenic genes.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Beyond enhancing β-oxidation, n-3 PUFAs concurrently suppress de novo lipogenesis by inhibiting the expression and maturation of SREBP-1, and by reducing the activity of ChREBP, thereby curbing hepatic glycolysis and lipid synthesis.34–37”
Citations
Cites
Iizuka, K., Bruick, R. K., Liang, G., Horton, J. D., & Uyeda, K. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401516101 · Cited by 834
A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver
Yamashita, H., Takenoshita, M., Sakurai, M., Bruick, R. K., Henzel, W. J., Shillinglaw, W., Arnot, D., & Uyeda, K. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161284298 · Cited by 682
Liang, G., Yang, J., Horton, J. D., Hammer, R. E., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111421200 · Cited by 669
REGULATION OF GENE EXPRESSION BY DIETARY FAT
Jump, D. Β., & Clarke, S. D. (1999) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.19.1.63 · Cited by 666
Jørgensen, S. B., Viollet, B., Andreelli, F., Frøsig, C., Birk, J. B., Schjerling, P., Vaulont, S., Richter, E. A., & Wojtaszewski, J. F. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306205200 · Cited by 553
ADD1/SREBP-1c Is Required in the Activation of Hepatic Lipogenic Gene Expression by Glucose
Foretz, M., Pacot, C., Dugail, I., Lemarchand, P., Guichard, C., Lièpvre, X. L., Lubrano-Berthelier, C., Spiegelman, B. M., Kim, J. B., Ferré, P., et al. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3760 · Cited by 548
The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity
Viollet, B., Andreelli, F., Jørgensen, S. B., Perrin, C., Geloen, A., Flamez, D., Mu, J., Lenzner, C., Baud, O., Bennoun, M., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16567 · Cited by 499
Xu, J., Nakamura, M. T., Cho, H. P., & Clarke, S. D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.33.23577 · Cited by 499
Dentin, R., Pégorier, J. P., Benhamed, F., Foufelle, F., Ferré, P., Fauveau, V., Magnuson, M. A., Girard, J. R., & Postic, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312475200 · Cited by 461
Self-citationUnsaturated Fatty Acids Down-regulate SREBP Isoforms 1a and 1c by Two Mechanisms in HEK-293 Cells
Hannah, V. C., Ou, J., Luong, A., Goldstein, J. L., & Brown, M. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007273200 · Cited by 448
Cited by
Sorted by citations
Postic, C., & Girard, J. R. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34275 · Cited by 1,243
Regulation of energy metabolism by long-chain fatty acids
Nakamura, M., Yudell, B. E., & Loor, J. J. (2013) · Progress in Lipid Research · doi:10.1016/j.plipres.2013.12.001 · Cited by 858
Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD)
Musso, G., Gambino, R. J., & Cassader, M. (2008) · Progress in Lipid Research · doi:10.1016/j.plipres.2008.08.001 · Cited by 691
Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum
Hardy, T., Oakley, F., Anstee, Q. M., & Day, C. P. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044224 · Cited by 641
From NAFLD to NASH to cirrhosis—new insights into disease mechanisms
Wree, A., Broderick, L., Canbay, A. E., Hoffman, H. M., & Feldstein, A. E. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.149 · Cited by 617
Metadata
- Authors
- Dentin, R.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Dentin, R.
- ORCID
- Dentin, R.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-10-01
- Volume
- 115
- Issue
- 10
- Pages
- 2843-2854
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1224299
- OpenAlex
- W2114472618
- Cited by
- 315
- References
- 50
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 11 · 2023: 15 · 2022: 12 · 2021: 15 · 2020: 19 · 2019: 8 · 2018: 14 · 2017: 14 · 2016: 18 · 2015: 19 · 2014: 9 · 2013: 23 · 2012: 13
- FWCI
- 16.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- European Commission (LSHMCT-2004-005272)
- Ministère de l'Enseignement Supérieur et de la Recherche
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- polyunsaturated fatty acids, ChREBP, nuclear translocation, hepatic glycolysis, lipogenesis, fatty acid synthase, mRNA degradation, xylulose-5-phosphate, pentose phosphate pathway, glucose metabolism, AMPK, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, saturated fatty acids, monounsaturated fatty acids, hepatocytes, transcriptional regulation
- MeSH terms
- Animals, Cells, Cultured, Dietary Fats, Unsaturated, Docosahexaenoic Acids, Glycolysis, Male, Multienzyme Complexes, Nuclear Proteins, Pentose Phosphate Pathway, Pyruvate Kinase, Transcription Factors, Eicosapentaenoic Acid, Down-Regulation, Gene Expression Regulation, Enzymologic, Protein Serine-Threonine Kinases, Hepatocytes, Lipogenesis, Mice, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, AMP-Activated Protein Kinases, Fatty Acid Synthases
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
