The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Docosahexaneoic acid (22:6,n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26S proteasome-dependent pathways
Open accessAbstract
Insulin induces and dietary n-3 PUFAs suppress hepatic de novo lipogenesis by controlling sterol-regulatory element binding protein-1 nuclear abundance (nSREBP-1). Our goal was to define the mechanisms involved in this regulatory process. Insulin treatment of rat primary hepatocytes rapidly augments nSREBP-1 and mRNA(SREBP-1c) while suppressing mRNA(Insig-2) but not mRNA(Insig-1). These events are preceded by rapid but transient increases in Akt and Erk phosphorylation. Removal of insulin from hepatocytes leads to a rapid decline in nSREBP-1 [half-time (T1/2) approximately 10 h] that is abrogated by inhibitors of 26S proteasomal degradation. 22:6,n-3, the major n-3 PUFA accumulating in livers of fish oil-fed rats, suppresses hepatocyte levels of nSREBP-1, mRNA(SREBP-1c), and mRNA(Insig-2) but modestly and transiently induces mRNA(Insig-1). More importantly, 22:6,n-3 accelerates the disappearance of hepatocyte nSREBP-1 (T1/2 approximately 4 h) through a 26S proteasome-dependent process. 22:6,n-3 has minimal effects on microsomal SREBP-1 and sterol-regulatory element binding protein cleavage-activating protein or nuclear SREBP-2. 22:6,n-3 transiently inhibits insulin-induced Akt phosphorylation but induces Erk phosphorylation. Inhibitors of Erk phosphorylation, but not overexpressed constitutively active Akt, rapidly attenuate 22:6,n-3 suppression of nSREBP-1. Thus, 22:6,n-3 suppresses hepatocyte nSREBP-1 through 26S proteasome- and Erk-dependent pathways. These studies reveal a novel mechanism for n-3 PUFA regulation of hepatocyte nSREBP-1 and lipid metabolism.
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.
Integrity signals
Registry
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.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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”
From The Impact of Omega-3 Fatty Acids on Triglyceride Levels in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-Analysis of Randomized Controlled Trials with Subgroup Analysis by Diabetes Status (2026) · cites this paper as [34]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In addition, n-3 FAs lead to intracellular degradation of apo B, which may be a result of decreased triglyceride availability or autophagic destruction of apo B via post-Golgi oxidation, 90 thereby diminishing the assembly of VLDL particles in the hepatocyte and decreasing VLDL secretion.91,92”
From Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association (2019) · cites this paper as [90]
Experimental — accuracy not yet measured
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
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15593 · Cited by 4,794
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092
Repa, J. J., Liang, G., Ou, J., Bashmakov, Y. K., Lobaccaro, J. A., Shimomura, I., Shan, B., Brown, M. S., Goldstein, J. L., & Mangelsdorf, D. J. (2000) · Genes & Development · doi:10.1101/gad.844900 · Cited by 1,724
Role of LXRs in control of lipogenesis
Schultz, J. R., Tu, H., Luk, A., Repa, J. J., Medina, J. C., Li, L., Schwendner, S., Wang, S., Thoolen, M., Mangelsdorf, D. J., et al. (2000) · Genes & Development · doi:10.1101/gad.850400 · Cited by 1,499
Metabolism of highly unsaturated n-3 and n-6 fatty acids
Sprecher, H. W. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s1388-1981(00)00077-9 · Cited by 894
Shimomura, I., Bashmakov, Y. K., Ikemoto, S., Horton, J. D., Brown, M. S., & Goldstein, J. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.24.13656 · Cited by 779
Chen, G., Liang, G., Ou, J., Goldstein, J. L., & Brown, M. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404297101 · Cited by 570
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
Ou, J., Tu, H., Shan, B., Luk, A. Y., DeBose‐Boyd, R. A., Bashmakov, Y. K., Goldstein, J. L., & Brown, M. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111138698 · Cited by 474
Adams, C. M., Reitz, J., Brabander, J. K. D., Feramisco, J. D., Li, L., Brown, M. S., & Goldstein, J. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410302200 · Cited by 463
Sundqvist, A., Bengoechea-Alonso, M. T., Ye, X., Lukiyanchuk, V., Jin, J., Harper, J. W., & Ericsson, J. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.04.010 · Cited by 457
Unsaturated 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
Dietary polyunsaturated fatty acids and regulation of gene transcription
Jump, D. Β. (2002) · Current Opinion in Lipidology · doi:10.1097/00041433-200204000-00007 · Cited by 441
Self-citationFatty Acid Regulation of Gene Transcription
Jump, D. Β. (2004) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360490278341 · Cited by 362
Self-citationWorgall, T. S., Sturley, S. L., Seo, T., Osborne, T. F., & Deckelbaum, R. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.40.25537 · Cited by 322
Liver-specific mRNA for Insig-2 down-regulated by insulin: Implications for fatty acid synthesis
Yabe, D., Komuro, R., Liang, G., Goldstein, J. L., & Brown, M. S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0130116100 · Cited by 296
Xu, J., Terán-Garcı́a, M., Park, J. H. Y., Nakamura, M., & Clarke, S. D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008973200 · Cited by 276
Tissue-specific, nutritional, and developmental regulation of rat fatty acid elongases
Wang, Y., Botolin, D., Christian, B., Busik, J. V., Xu, J., & Jump, D. Β. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m400335-jlr200 · Cited by 265
Self-citationRen, B., Thelen, A. P., Peters, J. M., Gonzalez, F. J., & Jump, D. Β. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.43.26827 · Cited by 264
Self-citationProtein Kinase B/Akt Prevents Fatty Acid-induced Apoptosis in Pancreatic β-Cells (INS-1)
Wrede, C. E., Dickson, L. M., Lingohr, M. K., Briaud, I., & Rhodes, C. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208756200 · Cited by 246
Control of Gene Expression by Fatty Acids
Pégorier, J. P., May, C. L., & Girard, J. R. (2004) · Journal of Nutrition · doi:10.1093/jn/134.9.2444s · Cited by 245
Fleischmann, M. M., & Iynedjian, P. B. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3490013 · Cited by 195
Mater, M. K., Thelen, A. P., Pan, D. A., & Jump, D. Β. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.46.32725 · Cited by 194
Self-citationOno, H., Shimano, H., Katagiri, H., Yahagi, N., Sakoda, H., Onishi, Y., Anai, M., Ogihara, T., Fujishiro, M., Viana, A. Y. I., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.12.2905 · Cited by 172
Roth, G., Kotzka, J., Kremer, L., Lehr, S., Lohaus, C., Meyer, H. E., Krone, W., & Müller‐Wieland, D. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005425200 · Cited by 157
Hirano, Y., Yoshida, M., Shimizu, M., & Sato, R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105200200 · Cited by 151
Cagen, L. M., Deng, X., Wilcox, H. G., PARK, E. A., Raghow, R., & Elam, M. B. (2004) · Biochemical Journal · doi:10.1042/bj20040162 · Cited by 150
The Role of Liver X Receptor-α in the Fatty Acid Regulation of Hepatic Gene Expression
Pawar, A., Botolin, D., Mangelsdorf, D. J., & Jump, D. Β. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307973200 · Cited by 149
Self-citationNagoshi, E., Imamoto, N., Sato, R., & Yoneda, Y. (1999) · Molecular Biology of the Cell · doi:10.1091/mbc.10.7.2221 · Cited by 128
Regulatory Role of Glycogen Synthase Kinase 3 for Transcriptional Activity of ADD1/SREBP1c
Kim, K. H., Song, M. J., Yoo, E. J., Choe, S. S., Park, S. D., & Kim, J. B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405522200 · Cited by 122
Regulation of the Rat SREBP-1c Promoter in Primary Rat Hepatocytes
Deng, X., Cagen, L. M., Wilcox, H. G., Park, E. A., Raghow, R., & Elam, M. B. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.6148 · Cited by 113
Sundqvist, A., & Ericsson, J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2335135100 · Cited by 85
Pawar, A., Xu, J., Jerks, E., Mangelsdorf, D. J., & Jump, D. Β. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206170200 · Cited by 80
Self-citationKeeton, A. B., Bortoff, K. D., Bennett, W. L., Franklin, J. L., Venable, D. Y., & Messina, J. L. (2003) · Endocrinology · doi:10.1210/en.2003-0592 · Cited by 75
Ribaux, P., & Iynedjian, P. B. (2003) · Biochemical Journal · doi:10.1042/bj20031287 · Cited by 60
Pan, D. A., Mater, M. K., Thelen, A. P., Peters, J. M., Gonzalez, F. J., & Jump, D. Β. (2000) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32383-x · Cited by 56
Self-citationBotolin, D., & Jump, D. Β. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212846200 · Cited by 42
Self-citationBennett, M. K., Toth, J. I., & Osborne, T. F. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404693200 · Cited by 33
NAKATANI, T., Katsumata, A., Miura, S., Kamei, Y., & Ezaki, O. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.07.003 · Cited by 25
Keeton, A. B., Bortoff, K. D., Franklin, J. L., & Messina, J. L. (2005) · Endocrinology · doi:10.1210/en.2004-1662 · Cited by 22
Cited by
Sorted by citations
The Opposing Effects of N-3 and n-6 Fatty Acids
Schmitz, G., & Ecker, J. (2008) · Progress in Lipid Research · doi:10.1016/j.plipres.2007.12.004 · Cited by 1,245
Fatty acid elongases in mammals: their regulation and roles in metabolism
JAKOBSSON, A., WESTERBERG, R., & JACOBSSON, A. (2006) · Progress in Lipid Research · doi:10.1016/j.plipres.2006.01.004 · Cited by 936
Skulas-Ray, A. C., Wilson, P. W. F., Harris, W. S., Brinton, E. A., Kris-Etherton, P. M., Richter, C. K., Jacobson, T. A., Engler, M. B., Miller, M., Robinson, J. G., et al. (2019) · Circulation · doi:10.1161/cir.0000000000000709 · Cited by 512
N-3 polyunsaturated fatty acid regulation of hepatic gene transcription
Jump, D. B. (2008) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3282ffaf6a · Cited by 443
Self-citationRole of trans fatty acids in the nutritional regulation of mammary lipogenesis in ruminants
Shingfield, K. J., Bernard, L., Leroux, C., & Chilliard, Y. (2010) · animal · doi:10.1017/s1751731110000510 · Cited by 403
Metadata
- Authors
- Botolin, D., Wang, Y., Christian, B., & Jump, D. B.
- Affiliations
- Michigan State University (US)
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 47
- Issue
- 1
- Pages
- 181-192
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC2764363
- OpenAlex
- W2164098551
- Cited by
- 162
- References
- 40
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 7 · 2016: 6 · 2015: 6 · 2014: 5 · 2013: 8 · 2012: 10
- FWCI
- 11.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Agriculture
- National Institutes of Health
- Cooperative State Research, Education, and Extension Service
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK043220)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- docosahexaenoic acid, omega-3 fatty acids, SREBP1, INSIG2, INSIG1, 26S proteasome, ERK1/2 phosphorylation, Akt phosphorylation, insulin signaling, hepatocytes, hepatic de novo lipogenesis, SREBP-1c, SREBP2, lipid metabolism
- MeSH terms
- Animals, Base Sequence, Cell Nucleus, Dietary Fats, Docosahexaenoic Acids, Insulin, Male, Membrane Proteins, Protease Inhibitors, RNA, Messenger, Rats, Sprague-Dawley, MAP Kinase Signaling System, Hepatocytes, Proteasome Endopeptidase Complex, Intracellular Signaling Peptides and Proteins, Lipid Metabolism, Rats, Sterol Regulatory Element Binding Protein 1, Proteasome Inhibitors
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
