ArticlePloS one2016
Generation of Mice with Hepatocyte-Specific Conditional Deletion of Notum.
Article in PloS one, 2016. 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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The trial behind it
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- WNT-β-catenin signalling in hepatocellular carcinoma: from bench to clinical trials.Nature reviews. Gastroenterology & hepatology · 2026Review
- Notum Deletion From Late-Stage Skeletal Cells Increases Cortical Bone Formation and Potentiates Skeletal Effects of Sclerostin Inhibition.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Structural Insights into Notum Covalent Inhibition.Journal of medicinal chemistry · 2021Article
- NOTUM promotes thermogenic capacity and protects against diet-induced obesity in male mice.Scientific reports · 2021Article
- Small-molecule inhibitors of carboxylesterase Notum.Future medicinal chemistry · 2021Review
- Article
- Carboxylesterase Notum Is a Druggable Target to Modulate Wnt Signaling.Journal of medicinal chemistry · 2021Article
- Progenitors oppositely polarize WNT activators and inhibitors to orchestrate tissue development.eLife · 2020Article
- Structural characterization of melatonin as an inhibitor of the Wnt deacylase Notum.Journal of pineal research · 2020Article
- Osteoblast-derived NOTUM reduces cortical bone mass in mice and theFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- A Strategy for Discovery of Endocrine Interactions with Application to Whole-Body Metabolism.Cell metabolism · 2018Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFine tuning of the Wnt/β-catenin signaling pathway is essential for the proper development and function of the liver. Aberrant activation of this pathway is observed in 20%-40% of hepatocellular carcinomas (HCC). Notum encodes a secreted Wnt deacylase that inhibits Wnt activity and thereby restricts the zone of activation of Wnt/β-catenin signaling. An important role of NOTUM has been described in development in drosophila, planaria and zebrafish, but its role in the mammalian liver is unknown. Notum is required for spatial control of the Wnt/β-catenin signaling in several animal models and the Wnt/β-catenin pathway contributes to liver patterning involved in metabolic zonation. Therefore, Notum may be involved in the liver patterning induced by the Wnt/β-catenin signaling during the adult stage. METHODOLOGY/PRINCIPAL
findingsWe generated a conditional Notum knockout mouse mutant to study the effect of the deletion of Notum in the liver. We show that Notum is a direct target of the Wnt/β-catenin signaling in the liver. Liver-specific deletion of Notum did not modify liver zonation, but Notum deletion had a long-term effect on mouse physiology. In particular, male mutant mice developed metabolic disorders.
conclusionWe show that Notum is not a key actor of Wnt/β-catenin-dependent liver patterning of adult mice, but has role in liver glucose homeostasis. Male mice deficient in Notum specifically in the liver develop metabolic dysfunctions implicating Notum in the development of Type 2 diabetes.
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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.