ArticleBritish journal of pharmacology2013
The β-catenin pathway contributes to the effects of leptin on SREBP-1c expression in rat hepatic stellate cells and liver fibrosis.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 75 citations in OpenAlex.
- Contribution of p38 MAPK in liver fibrosis: An overview of mechanisms, signaling pathways, and therapeutic targets (Review).International journal of molecular medicine · 2026Review
- Statins as anti-tumor agents: A paradigm for repurposed drugs.Cancer reports (Hoboken, N.J.) · 2024Review
- SREBP Regulation of Lipid Metabolism in Liver Disease, and Therapeutic Strategies.Biomedicines · 2023Review
- The effect of different boron compounds on nutrient digestibility, intestinal nutrient transporters, and liver lipid metabolism.Turkish journal of medical sciences · 2023Article
- Crosstalk of hepatocyte nuclear factor 4a and glucocorticoid receptor in the regulation of lipid metabolism in mice fed a high-fat-high-sugar diet.Lipids in health and disease · 2022Article
- miR-139-5p sponged by LncRNA NEAT1 regulates liver fibrosis via targeting β-catenin/SOX9/TGF-β1 pathway.Cell death discovery · 2021Article
- Role of Leptin in the Digestive System.Frontiers in pharmacology · 2021Review
- β-catenin mediates the effect of GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose diet.European journal of histochemistry : EJH · 2020Article
- MicroRNA-10a Impairs Liver Metabolism in Hepatitis C Virus-Related Cirrhosis Through Deregulation of the Circadian Clock Gene Brain and Muscle Aryl Hydrocarbon Receptor Nuclear Translocator-Like 1.Hepatology communications · 2019Article
- Antifibrotics in liver disease: are we getting closer to clinical use?Hepatology international · 2019Review
- Hepatic IRS1 and ß-catenin expression is associated with histological progression and overt diabetes emergence in NAFLD patients.Journal of gastroenterology · 2018Article
- Hippocampal PPARα is a novel therapeutic target for depression and mediates the antidepressant actions of fluoxetine in mice.British journal of pharmacology · 2018Article
- Leptin-induced inflammation by activating IL-6 expression contributes to the fibrosis and hypertrophy of ligamentum flavum in lumbar spinal canal stenosis.Bioscience reports · 2018Article
- Advances in therapeutic options for portal hypertension.Therapeutic advances in gastroenterology · 2018Review
- NADPH Oxidase Signaling Pathway Mediates Mesenchymal Stem Cell-Induced Inhibition of Hepatic Stellate Cell Activation.Stem cells international · 2018Article
- SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.Nature reviews. Endocrinology · 2017Review
- Hepatic stellate cells as key target in liver fibrosis.Advanced drug delivery reviews · 2017Review
- Modified SJH alleviates FFAs-induced hepatic steatosis through leptin signaling pathways.Scientific reports · 2017Article
- GATA binding protein 3 is correlated with leptin regulation of PPARγ1 in hepatic stellate cells.Journal of cellular and molecular medicine · 2017Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeLiver fibrosis is commonly associated with obesity and most obese patients develop hyperleptinaemia. The adipocytokine leptin has a unique role in the development of liver fibrosis. Activation of hepatic stellate cells (HSCs) is a key step in hepatic fibrogenesis and sterol regulatory element-binding protein-1c (SREBP-1c) can inhibit HSC activation. We have shown that leptin strongly inhibits SREBP-1c expression in rat HSCs. Hence, we aimed to clarify whether the β-catenin pathway, the crucial negative regulator of adipocyte differentiation, mediates the effects of leptin on SREBP-1c expression in HSCs and in mouse liver fibrosis. EXPERIMENTAL APPROACH: HSCs were prepared from rats and mice. Gene expressions were analysed by real-time PCR, Western blot analysis, immunostaining and transient transfection assays. KEY
resultsLeptin increased β-catenin protein but not mRNA levels in cultured HSCs. Leptin induced phosphorylation of glycogen synthase kinase-3β at Ser(9) and subsequent stabilization of β-catenin protein was mediated, at least in part, by ERK and p38 MAPK pathways. The leptin-induced β-catenin pathway reduced SREBP-1c expression and activity but did not affect protein levels of key regulators controlling SREBP-1c activity, and was not involved in leptin inhibition of liver X receptor α. In a mouse model of liver injury, the β-catenin pathway was shown to be involved in leptin-induced liver fibrosis. CONCLUSIONS AND IMPLICATIONS: The β-catenin pathway contributes to leptin regulation of SREBP-1c expression in HSCs and leptin-induced liver fibrosis in mice. These results have potential implications for clarifying the mechanisms of liver fibrogenesis associated with elevated leptin levels.
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