ArticleJournal of lipid research2006
Docosahexaneoic acid (22:6,n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26S proteasome-dependent pathways.
Article in Journal of lipid research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 164 citations in OpenAlex.
- Effects of oral eicosapentaenoic acid versus docosahexaenoic acid on human peripheral blood mononuclear cell gene expression.Atherosclerosis · 2015Trial
- 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.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Maternal docosahexaenoic acid and eicosapentaenoic acid supplementation: effects and mechanisms on lipid metabolism in the offspring.Frontiers in nutrition · 2026Review
- Beneficial Effects of Omega-3 Fatty Acids on Obesity and Related Metabolic and Chronic Inflammatory Diseases.Nutrients · 2025Review
- Eicosapentaenoic acid increases proportion of type 1 muscle fibers through PPARδ and AMPK pathways in rats.iScience · 2024Article
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- Changes in the Lipid Metabolism of theMetabolites · 2023Article
- The interplay between dietary fatty acids and gut microbiota influences host metabolism and hepatic steatosis.Nature communications · 2023Article
- Nonalcoholic Fatty Liver Disease and Omega-3 Fatty Acids: Mechanisms and Clinical Use.Annual review of nutrition · 2023Review
- Key events in cancer: Dysregulation of SREBPs.Frontiers in pharmacology · 2023Review
- Composition of Fatty Acids and Localization ofAnimals : an open access journal from MDPI · 2022Article
- Controversies in the Use of Omega-3 Fatty Acids to Prevent Atherosclerosis.Current atherosclerosis reports · 2022Review
- The Effects of Probiotics and Omega-3 Fatty Acids in Liver Steatosis Induced in Rats by High-Fructose Corn Syrup.International journal of clinical practice · 2022Article
- Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations.Communications biology · 2021Article
- From Food to Genes: Transcriptional Regulation of Metabolism by Lipids and Carbohydrates.Nutrients · 2021Review
- Nonalcoholic fatty liver disease stratification by liver lipidomics.Journal of lipid research · 2021Article
- Article
- Molecular Characterization, Nutritional and Insulin Regulation of Elovl6 in Rainbow Trout (Biomolecules · 2020Article
- Bioactive Compounds for the Management of Hypertriglyceridemia: Evidence From Clinical Trials and Putative Action Targets.Frontiers in nutrition · 2020Review
- Proton NMR Enables the Absolute Quantification of Aqueous Metabolites and Lipid Classes in Unique Mouse Liver Samples.Metabolites · 2019Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.