ArticleFrontiers in pharmacology2018
The Wnt Signaling Pathway Effector TCF7L2 Mediates Olanzapine-Induced Weight Gain and Insulin Resistance.
Article in Frontiers in pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- Article
- Olanzapine-Induced Diabetic Ketoacidosis and Neuroleptic Malignant Syndrome: A Case Report.Cureus · 2025Article
- Olanzapine and peripheral metabolic dysregulation: organ-resolved mechanisms, risk, and MASLD-aligned care pathways.Frontiers in pharmacology · 2025Review
- Genetic Predisposition to Prediabetes in the Kazakh Population.Current issues in molecular biology · 2024Article
- LRP6 Bidirectionally Regulates Insulin Sensitivity through Insulin Receptor and S6K Signaling in Rats with CG-IUGR.Current medical science · 2023Article
- Olanzapine decreased osteocyte maturation and Wnt/β-catenin signaling during loading of the alveolar bone in rats.Biomolecules & biomedicine · 2023Article
- Oviduct Transcriptomic Reveals the Regulation of mRNAs and lncRNAs Related to Goat Prolificacy in the Luteal Phase.Animals : an open access journal from MDPI · 2022Article
- MicroRNA-22-3p targeted regulating transcription factor 7-like 2 (TCF7L2) constrains the Wnt/β-catenin pathway and malignant behavior in osteosarcoma.Bioengineered · 2022Article
- Olanzapine Promotes the Occurrence of Metabolic Disorders in Conditional TCF7L2-Knockout Mice.Frontiers in cell and developmental biology · 2022Article
- 5:2 intermittent fasting tapers food intake in the refeeding state and ameliorates metabolic disturbances in mice exposed to olanzapine.Frontiers in psychiatry · 2022Article
- Metformin ameliorates olanzapine-induced obesity and glucose intolerance by regulating hypothalamic inflammation and microglial activation in female mice.Frontiers in pharmacology · 2022Article
- Changes of LRP6/β-catenin pathway in adipose tissue of rats with intrauterine growth restriction with catch-up growth.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Article
- Transcription Factor-7-Like-2 (TCF7L2) in Atherosclerosis: A Potential Biomarker and Therapeutic Target.Frontiers in cardiovascular medicine · 2021Review
- Drug Repurposing in Dentistry; towards Application of Small Molecules in Dentin Repair.International journal of molecular sciences · 2020Article
- Olanzapine-Induced Activation of Hypothalamic Astrocytes and Toll-Like Receptor-4 Signaling via Endoplasmic Reticulum Stress Were Related to Olanzapine-Induced Weight Gain.Frontiers in neuroscience · 2020Article
- Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain.Cells · 2019Review
- Type 2 Diabetes-Associated Genetic Polymorphisms as Potential Disease Predictors.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Review
- TCF7L2 regulates pancreatic β-cell function through PI3K/AKT signal pathway.Diabetology & metabolic syndrome · 2019Article
- Genetic associations between Transcription Factor 7 Like 2 rs7903146 polymorphism and type 2 diabetes mellitus: a meta-analysis of 115,809 subjects.Diabetology & metabolic syndrome · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Olanzapine is a widely used atypical antipsychotic medication for treatment of schizophrenia and is often associated with serious metabolic abnormalities including weight gain and impaired glucose tolerance. These metabolic side effects are severe clinical problems but the underpinning mechanism remains poorly understood. Recently, growing evidence suggests that Wnt signaling pathway has a critical role in the pathogenesis of schizophrenia and molecular cascades of antipsychotics action, of which Wnt signaling pathway key effector TCF7L2 is strongly associated with glucose homeostasis. In this study, we aim to explore the characteristics of metabolic disturbance induced by olanzapine and to elucidate the role of TCF7L2 in this process. C57BL/6 mice were subject to olanzapine (4 mg/kg/day), or olanzapine plus metformin (150 mg/kg/day), or saline, respectively, for 8 weeks. Metabolic indices and TCF7L2 expression levels in liver, skeletal muscle, adipose, and pancreatic tissues were closely monitored. Olanzapine challenge induced remarkably increased body weight, fasting insulin, homeostasis model assessment-insulin resistance index, and TCF7L2 protein expression in liver, skeletal muscle, and adipose tissues. Notably, these effects could be effectively ameliorated by metformin. In addition, we found that olanzapine-induced body weight gain and insulin resistance actively influence the expression of TCF7L2 in liver and skeletal muscle, and elevated level of insulin determines the increased expression of TCF7L2 in adipose tissue. Our results demonstrate that TCF7L2 participates in olanzapine-induced metabolic disturbance, which presents a novel mechanism for olanzapine-induced metabolic disturbance and a potential therapeutic target to prevent the associated metabolic side effects.
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