ArticleProceedings of the National Academy of Sciences of the United States of America2004
Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers.
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Who cites it
235 citing papers in PubMed, 537 citations in OpenAlex.
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- Spirulina Preconditioning Attenuates Ischemia-Reperfusion Injury in a Steatotic Rat Liver Model.Antioxidants (Basel, Switzerland) · 2026Article
- Mechanism-based new approach methodologies for in vitro detection of chemical-induced liver steatosis.Archives of toxicology · 2026Review
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- The association between visceral fat accumulation caused by high-dose folic acid supplementation in the first trimester and gestational diabetes mellitus: protocol for a nested case-control study in a cohort study.BMC pregnancy and childbirth · 2025Article
- Widespread discordance between mRNA expression, protein abundance andbioRxiv : the preprint server for biology · 2025Article
- Postbiotic potential of SCFAs on metaflammation and gut microbiota alteration in diabetes.Journal of biosciences · 2025Article
- Glycerol Kinase Drives Hepatic de novo Lipogenesis and Triglyceride Synthesis in Nonalcoholic Fatty Liver by Activating SREBP-1c Transcription, Upregulating DGAT1/2 Expression, and Promoting Glycerol Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- LXR-dependent enhancer activation regulates the temporal organization of the liver's response to refeeding leading to lipogenic gene overshoot.PLoS biology · 2024Article
- Phosphorylation of Insig-2 mediates inhibition of fatty acid synthesis by polyunsaturated fatty acids.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Oligonucleotide therapies for nonalcoholic steatohepatitis.Molecular therapy. Nucleic acids · 2024Review
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- Therapeutic potential of oleic acid supplementation in myotonic dystrophy muscle cell models.Biological research · 2024Article
- Research progress, challenges and perspectives of phospholipids metabolism in the LXR‑LPCAT3 signaling pathway and its relation to NAFLD (Review).International journal of molecular medicine · 2024Review
- Cornelian Cherry (International journal of molecular sciences · 2024Article
- Nonalcoholic Fatty Liver Disease and Staging of Hepatic Fibrosis.Advances in experimental medicine and biology · 2024Review
- Hepatic macrophage niche: a bridge between HBV-mediated metabolic changes with intrahepatic inflammation.Frontiers in immunology · 2024Review
- Effects of high intensity interval vs. low intensity continuous training on LXRβ, ABCG5 and ABCG8 genes expression in male wistar rats.ARYA atherosclerosis · 2024Article
- Feeding sows milk biofortified with n-6 and n-3 modulates immune status of sows and drives positive transgenerational effects.PloS one · 2024Article
175 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Transcription of the gene encoding sterol regulatory element-binding protein 1c (SREBP-1c) is known to be activated by insulin in the liver. The resultant SREBP-1c protein activates transcription of the genes required for fatty acid synthesis. Here, we use SREBP-1c promoter reporter constructs to dissect the mechanism of insulin activation in freshly isolated rat hepatocytes. The data show that a complete insulin response (increase of 6- to 11-fold) requires two binding sites for liver X receptors (LXRs), which are nuclear receptors that are activated by oxygenated sterols. Disruption of these binding sites did not lower basal transcription but severely reduced the response to insulin. In contrast, disruption of the closely linked binding sites for SREBPs and nuclear factor Y lowered basal transcription drastically but still permitted a 4- to 7-fold increase in response to insulin. Arachidonic acid, an inhibitor of LXR activation, blocked the response to insulin. We conclude that insulin activates the SREBP-1c promoter primarily by increasing the activity of LXRs, possibly through production of a ligand that activates LXRs or their heterodimerizing partner, the retinoid X receptor. Nuclear SREBPs and nuclear factor Y play permissive roles.
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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.