ArticleAutophagy2017
Loss of ULK1 increases RPS6KB1-NCOR1 repression of NR1H/LXR-mediated Scd1 transcription and augments lipotoxicity in hepatic cells.
Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- The pivotal role of SCD1 in digestive cancers: Bridging lipid metabolic reprogramming and programmed cell death (Review).International journal of oncology · 2026Review
- The ULK1-NCOA3 axis restrains de novo lipogenesis and prevents diet-induced steatohepatitis and fibrosis in mice.The Journal of clinical investigation · 2026Article
- Polystyrene nanoplastics induce hepatic steatosis by disrupting autophagic degradation of NCoR1 and suppressing PPARα-mediated fatty acid oxidation.Journal of nanobiotechnology · 2026Article
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Liver Metabolism at the Crossroads: The Reciprocal Control of Nutrient-Sensing Nuclear Receptors and Autophagy.International journal of molecular sciences · 2025Review
- The nonautophagic functions of autophagy-related proteins.Autophagy · 2024Review
- Targeting nuclear receptors for NASH/MASH: From bench to bedside.Liver research (Beijing, China) · 2024Article
- A review of experimental and clinical studies on the therapeutic effects of pomegranate (Food science & nutrition · 2023Review
- Review
- Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis.Autophagy · 2023Article
- Review
- Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications.Acta pharmaceutica Sinica. B · 2022Review
- ULK1 Signaling in the Liver: Autophagy Dependent and Independent Actions.Frontiers in cell and developmental biology · 2022Review
- SCD1, autophagy and cancer: implications for therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Bioactivity Screening of Antarctic Sponges Reveals Anticancer Activity and Potential Cell Death via Ferroptosis by Mycalols.Marine drugs · 2021Article
- HIF-1α downregulation of miR-433-3p in adipocyte-derived exosomes contributes to NPC progression via targeting SCD1.Cancer science · 2021Article
- Ghrelin-Mediated Regeneration and Plasticity After Nervous System Injury.Frontiers in cell and developmental biology · 2021Review
- The Role and Mechanism of Oxidative Stress and Nuclear Receptors in the Development of NAFLD.Oxidative medicine and cellular longevity · 2021Review
- Loss of ULK1 Attenuates Cholesterogenic Gene Expression in Mammalian Hepatic Cells.Frontiers in cell and developmental biology · 2020Article
- Hepatic Lipid Catabolism via PPARα-Lysosomal Crosstalk.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Lipotoxicity caused by saturated fatty acids (SFAs) induces tissue damage and inflammation in metabolic disorders. SCD1 (stearoyl-coenzyme A desaturase 1) converts SFAs to mono-unsaturated fatty acids (MUFAs) that are incorporated into triglycerides and stored in lipid droplets. SCD1 thus helps protect hepatocytes from lipotoxicity and its reduced expression is associated with increased lipotoxic injury in cultured hepatic cells and mouse models. To further understand the role of SCD1 in lipotoxicity, we examined the regulation of Scd1 in hepatic cells treated with palmitate, and found that NR1H/LXR (nuclear receptor subfamily 1 group H) ligand, GW3965, induced Scd1 expression and lipid droplet formation to improve cell survival. Surprisingly, ULK1/ATG1 (unc-51 like kinase) played a critical role in protecting hepatic cells from SFA-induced lipotoxicity via a novel mechanism that did not involve macroautophagy/autophagy. Specific loss of Ulk1 blocked the induction of Scd1 gene transcription by GW3965, decreased lipid droplet formation, and increased apoptosis in hepatic cells exposed to palmitate. Knockdown of ULK1 increased RPS6KB1 (ribosomal protein S6 kinase, polypeptide 1) signaling that, in turn, induced NCOR1 (nuclear receptor co-repressor 1) nuclear uptake, interaction with NR1H/LXR, and recruitment to the Scd1 promoter. These events abrogated the stimulation of Scd1 gene expression by GW3965, and increased lipotoxicity in hepatic cells. In summary, we have identified a novel autophagy-independent role of ULK1 that regulates NR1H/LXR signaling, Scd1 expression, and intracellular lipid homeostasis in hepatic cells exposed to a lipotoxic environment.
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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.