ArticleScientific reports2020
Activation of GPR40 induces hypothalamic neurogenesis through p38- and BDNF-dependent mechanisms.
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 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Adipose Tissue-Central Nervous System Axis in Obesity: Molecular Mechanisms, Inflammation, and Nutritional and Technological Implications.Metabolites · 2026Review
- A Lipid Road to Neuroimmunology: Fatty Acids Linking Immune and Nervous Systems.Neuroimmunomodulation · 2026Review
- Metabolic sexual dimorphism in hypothalamic Fezf1 neuron-specific BDNF knockout.Biology of sex differences · 2025Article
- Antihypertensive Drug Amlodipine Besylate Shows Potential in Alleviating Diabetic Peripheral Neuropathy.Diabetes · 2025Article
- Fish Oil Supplementation Attenuates Offspring's Neurodevelopmental Changes Induced by a Maternal High-Fat Diet in a Rat Model.Nutrients · 2025Article
- Metabolite-Sensing Receptors: Emerging Targets for Modulating Chronic Pain Pathways.Current issues in molecular biology · 2025Review
- 4-Hydroxynonenal from Mitochondrial and Dietary Sources Causes Lysosomal Cell Death for Lifestyle-Related Diseases.Nutrients · 2024Review
- Enhanced Activation of the S1PR2-IL-1β-Src-BDNF-TrkB Pathway Mediates Neuroinflammation in the Hippocampus and Cognitive Impairment in Hyperammonemic Rats.International journal of molecular sciences · 2023Article
- Article
- Adult neurogenesis and aging mechanisms: a collection of insights.Scientific reports · 2023Article
- G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.Signal transduction and targeted therapy · 2023Review
- Learn from failures and stay hopeful to GPR40, a GPCR target with robust efficacy, for therapy of metabolic disorders.Frontiers in pharmacology · 2022Review
- Mini review: The relationship between energy status and adult hippocampal neurogenesis.Neuroscience letters · 2021Review
- GPR40 receptor agonist TAK-875 improves cognitive deficits and reduces β-amyloid production in APPswe/PS1dE9 mice.Psychopharmacology · 2021Article
- Mercury Toxicity and Neurogenesis in the Mammalian Brain.International journal of molecular sciences · 2021Review
- Microglia Regulate Neuronal Circuits in Homeostatic and High-Fat Diet-Induced Inflammatory Conditions.Frontiers in cellular neuroscience · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypothalamic adult neurogenesis provides the basis for renewal of neurons involved in the regulation of whole-body energy status. In addition to hormones, cytokines and growth factors, components of the diet, particularly fatty acids, have been shown to stimulate hypothalamic neurogenesis; however, the mechanisms behind this action are unknown. Here, we hypothesized that GPR40 (FFAR1), the receptor for medium and long chain unsaturated fatty acids, could mediate at least part of the neurogenic activity in the hypothalamus. We show that a GPR40 ligand increased hypothalamic cell proliferation and survival in adult mice. In postnatal generated neurospheres, acting in synergy with brain-derived neurotrophic factor (BDNF) and interleukin 6, GPR40 activation increased the expression of doublecortin during the early differentiation phase and of the mature neuronal marker, microtubule-associated protein 2 (MAP2), during the late differentiation phase. In Neuro-2a proliferative cell-line GPR40 activation increased BDNF expression and p38 activation. The chemical inhibition of p38 abolished GPR40 effect in inducing neurogenesis markers in neurospheres, whereas BDNF immunoneutralization inhibited GPR40-induced cell proliferation in the hypothalamus of adult mice. Thus, GPR40 acts through p38 and BDNF to induce hypothalamic neurogenesis. This study provides mechanistic advance in the understating of how a fatty acid receptor regulates adult hypothalamic neurogenesis.
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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.