ArticleScientific reports2020
Insulin activates hepatic Wnt/β-catenin signaling through stearoyl-CoA desaturase 1 and Porcupine.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk.Genes & diseases · 2024Review
- A comparative study of the therapeutic effect of bone marrow mesenchymal stem cells versus insulin on mandibular dento-alveolar complex collagen formation and beta-catenin expression in experimentally induced type I diabetes.The Saudi dental journal · 2023Article
- Wnt signaling preserves progenitor cell multipotency during adipose tissue development.Nature metabolism · 2023Article
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- Article
- Early-life starvation alters lipid metabolism in adults to cause developmental pathology in Caenorhabditis elegans.Genetics · 2023Article
- A role for β-catenin in diet-induced skeletal muscle insulin resistance.Physiological reports · 2023Article
- Liraglutide Attenuates Hepatic Oxidative Stress, Inflammation, and Apoptosis in Streptozotocin-Induced Diabetic Mice by Modulating the Wnt/Mediators of inflammation · 2023Article
- Wnt/β-Catenin Signaling as a Driver of Stemness and Metabolic Reprogramming in Hepatocellular Carcinoma.Cancers · 2022Review
- Article
- Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis.Frontiers in oncology · 2022Review
- Dysregulation of BMP, Wnt, and Insulin Signaling in Fragile X Syndrome.Frontiers in cell and developmental biology · 2022Review
- Stearoyl-CoA desaturase 5 (SCD5), a Δ-9 fatty acyl desaturase in search of a function.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Wnt/β-catenin pathway plays a pivotal role in liver structural and metabolic homeostasis. Wnt activity is tightly regulated by the acyltransferase Porcupine through the addition of palmitoleate. Interestingly palmitoleate can be endogenously produced by the stearoyl-CoA desaturase 1 (SCD1), a lipogenic enzyme transcriptionally regulated by insulin. This study aimed to determine whether nutritional conditions, and insulin, regulate Wnt pathway activity in liver. An adenoviral TRE-Luciferase reporter was used as a readout of Wnt/β-catenin pathway activity, in vivo in mouse liver and in vitro in primary hepatocytes. Refeeding enhanced TRE-Luciferase activity and expression of Wnt target genes in mice liver, revealing a nutritional regulation of the Wnt/β-catenin pathway. This effect was inhibited in liver specific insulin receptor KO (iLIRKO) mice and upon wortmannin or rapamycin treatment. Overexpression or inhibition of SCD1 expression regulated Wnt/β-catenin activity in primary hepatocytes. Similarly, palmitoleate added exogenously or produced by SCD1-mediated desaturation of palmitate, induced Wnt signaling activity. Interestingly, this effect was abolished in the absence of Porcupine, suggesting that both SCD1 and Porcupine are key mediators of insulin-induced Wnt/β-catenin activity in hepatocytes. Altogether, our findings suggest that insulin and lipogenesis act as potential novel physiological inducers of hepatic Wnt/β-catenin pathway.
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