ArticleThe Biochemical journal2012
Hypothalamic glycogen synthase kinase 3β has a central role in the regulation of food intake and glucose metabolism.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 88 citations in OpenAlex.
- A Combined GLP-1/PPARa/CB1-Based Therapy to Restore the Central and Peripheral Metabolic Dysregulation Induced by a High-Fructose High-Fat Diet.International journal of molecular sciences · 2025Article
- The effects of moderate alcohol and THC co-use during male and female rat adolescence on AKT-GSK3ß signaling in adulthood.Behavioural brain research · 2025Article
- Animal models of haploinsufficiency revealed the isoform-specific role of GSK-3 in HFD-induced obesity and glucose intolerance.American journal of physiology. Cell physiology · 2024Article
- Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments.Biology of sex differences · 2024Article
- Conditional Deletion of β-Catenin in the Mediobasal Hypothalamus Impairs Adaptive Energy Expenditure in Response to High-Fat Diet and Exacerbates Diet-Induced Obesity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- GSK-3 at the heart of cardiometabolic diseases: Isoform-specific targeting is critical to therapeutic benefit.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- Ependyma in Neurodegenerative Diseases, Radiation-Induced Brain Injury and as a Therapeutic Target for Neurotrophic Factors.Biomolecules · 2023Review
- Phosphoproteomics reveals rewiring of the insulin signaling network and multi-nodal defects in insulin resistance.Nature communications · 2023Article
- Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases.Medicinal research reviews · 2022Review
- Article
- Glucocorticoids Influencing Wnt/β-Catenin Pathway; Multiple Sites, Heterogeneous Effects.Molecules (Basel, Switzerland) · 2020Review
- Overexpression of GSK-3β in Adult Tet-OFF GSK-3β Transgenic Mice, and Not During Embryonic or Postnatal Development, Induces Tau Phosphorylation, Neurodegeneration and Learning Deficits.Frontiers in molecular neuroscience · 2020Article
- Caloric Restriction and Ketogenic Diet Therapy for Epilepsy: A Molecular Approach InvolvingFrontiers in neurology · 2020Review
- Mitochondrial damage by α-synuclein causes cell death in human dopaminergic neurons.Cell death & disease · 2019Article
- Hypothalamic leptin sensitivity and health benefits of time-restricted feeding are dependent on the time of day in male mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Casein kinase 1-epsilon deletion increases mu opioid receptor-dependent behaviors and binge eating1.Genes, brain, and behavior · 2017Article
- Leptin Induces Mitosis and Activates the Canonical Wnt/β-Catenin Signaling Pathway in Neurogenic Regions ofFrontiers in endocrinology · 2017Article
- Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis.The Journal of biological chemistry · 2016Article
- Wnt3a upregulates brain-derived insulin by increasing NeuroD1 via Wnt/β-catenin signaling in the hypothalamus.Molecular brain · 2016Article
- Hypothalamic Wnt Signalling and its Role in Energy Balance Regulation.Journal of neuroendocrinology · 2016Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
GSK3β (glycogen synthase kinase 3β) is a ubiquitous kinase that plays a key role in multiple intracellular signalling pathways, and increased GSK3β activity is implicated in disorders ranging from cancer to Alzheimer's disease. In the present study, we provide the first evidence of increased hypothalamic signalling via GSK3β in leptin-deficient Lep(ob/ob) mice and show that intracerebroventricular injection of a GSK3β inhibitor acutely improves glucose tolerance in these mice. The beneficial effect of the GSK3β inhibitor was dependent on hypothalamic signalling via PI3K (phosphoinositide 3-kinase), a key intracellular mediator of both leptin and insulin action. Conversely, neuron-specific overexpression of GSK3β in the mediobasal hypothalamus exacerbated the hyperphagia, obesity and impairment of glucose tolerance induced by a high-fat diet, while having little effect in controls fed standard chow. These results demonstrate that increased hypothalamic GSK3β signalling contributes to deleterious effects of leptin deficiency and exacerbates high-fat diet-induced weight gain and glucose intolerance.
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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.