ArticleEMBO reports2023
Fasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Combinatorial targeting of the miR-379/miR-410 cluster normalizes glucose and lipid homeostasis in male models of diabetes and obesity.Nature communications · 2026Article
- Ubc9-Mediated SUMOylation of RPL3, an Unappreciated Mechanism against Hepatocyte Senescence by Repressing the DHX9-p16 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TSC22D1 is a newly identified inhibitor of insulin secretion in pancreatic beta cells.The FEBS journal · 2025Article
- Emerging Roles of Post-Translational Modifications in Metabolic Homeostasis and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- The ubiquitin-proteasome system: A potential target for the MASLD.Acta pharmaceutica Sinica. B · 2025Review
- Knocking down tumor suppressor gene PTPRG enhances axonal regeneration of dorsal root ganglion neurons.Frontiers in cell and developmental biology · 2025Article
- SUMOylation at the crossroads of gut health: insights into physiology and pathology.Cell communication and signaling : CCS · 2024Review
- Abnormal protein SUMOylation in liver disease: novel target for therapy.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Tissue adaptation to metabolic stress: insights from SUMOylation.Frontiers in endocrinology · 2024Review
- Article
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
Accumulation of excess nutrients hampers proper liver function and is linked to nonalcoholic fatty liver disease (NAFLD) in obesity. However, the signals responsible for an impaired adaptation of hepatocytes to obesogenic dietary cues remain still largely unknown. Post-translational modification by the small ubiquitin-like modifier (SUMO) allows for a dynamic regulation of numerous processes including transcriptional reprogramming. We demonstrate that specific SUMOylation of transcription factor Prox1 represents a nutrient-sensitive determinant of hepatic fasting metabolism. Prox1 is highly SUMOylated on lysine 556 in the liver of ad libitum and refed mice, while this modification is abolished upon fasting. In the context of diet-induced obesity, Prox1 SUMOylation becomes less sensitive to fasting cues. The hepatocyte-selective knock-in of a SUMOylation-deficient Prox1 mutant into mice fed a high-fat/high-fructose diet leads to a reduction of systemic cholesterol levels, associated with the induction of liver bile acid detoxifying pathways during fasting. The generation of tools to maintain the nutrient-sensitive SUMO-switch on Prox1 may thus contribute to the development of "fasting-based" approaches for the preservation of metabolic health.
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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.