ArticleMolecular psychiatry2021
Leptin regulates exon-specific transcription of the Bdnf gene via epigenetic modifications mediated by an AKT/p300 HAT cascade.
Article in Molecular psychiatry, 2021. 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, 55 citations in OpenAlex.
- Intermittent Fasting Enhances Genome Integrity and Cytoprotective Pathways via (BHB) β-Hydroxybutyrate Signaling and Chromatin Remodeling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Parallel Pathways, Divergent Outcomes: Adipose Tissue-Neural Crosstalk in Depression and Obesity.Journal of clinical medicine · 2025Review
- Metabolic reprogramming in ischemic stroke: when glycolytic overdrive meets lipid storm.Cell death & disease · 2025Review
- AKT signaling upregulates BDNF expression in induced neural stem cells that interact with microglia.Stem cell research & therapy · 2025Article
- Visceral adipose tissue-derived extracellular vesicles promote stress susceptibility in obese mice via miR-140-5p.Acta pharmacologica Sinica · 2025Article
- Alleviation of Microglia Mediating Hippocampal Neuron Impairments and Depression-Related Behaviors by Urolithin B via the SIRT1-FOXO1 Pathway.CNS neuroscience & therapeutics · 2025Article
- Hippocampal Leptin Resistance and Cognitive Decline: Mechanisms, Therapeutic Strategies and Clinical Implications.Biomedicines · 2024Review
- The interaction of BDNF with estrogen in the development of hypertension and obesity, particularly during menopause.Frontiers in endocrinology · 2024Review
- Medial prefrontal cortical PPM1F alters depression-related behaviors by modifying p300 activity via the AMPK signaling pathway.CNS neuroscience & therapeutics · 2023Article
- Role of Hippocampal miR-132-3p in Modifying the Function of Protein Phosphatase Mg2+/Mn2+-dependent 1 F in Depression.Neurochemical research · 2023Article
- Article
- The colonic interleukin-19 aggravates the dextran sodium sulfate/stress-induced comorbidities due to colitis and anxiety.Frontiers in immunology · 2023Article
- Leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence.Molecular psychiatry · 2022Article
- Gm364 coordinates MIB2/DLL3/Notch2 to regulate female fertility through AKT activation.Cell death and differentiation · 2022Article
- First Account of Psychological Changes Perceived by a Female with Congenital Leptin Deficiency upon Treatment with Metreleptin.Obesity facts · 2022Article
- Prenatal Iron Deficiency and Choline Supplementation Interact to Epigenetically RegulateNutrients · 2021Article
- PPM1F in Dentate Gyrus Modulates Anxiety-Related Behaviors by Regulating BDNF Expression via AKT/JNK/p-H3S10 Pathway.Molecular neurobiology · 2021Article
- Cryptotanshinone ameliorates CUS-induced depressive-like behaviors in mice.Translational neuroscience · 2021Article
- Dysregulated gene-associated biomarkers for Alzheimer's disease and aging.Translational neuroscience · 2021Article
- BDNF levels in adolescent patients with anorexia nervosa increase continuously to supranormal levels 2.5 years after first hospitalization.Journal of psychiatry & neuroscience : JPNArticle
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Leptin is an adipocyte-derived hormone with pleiotropic functions affecting appetite and mood. While leptin's role in the regulation of appetite has been extensively studied in hypothalamic neurons, its function in the hippocampus, where it regulates mood-related behaviors, is poorly understood. Here, we show that the leptin receptor (LepRb) colocalizes with brain-derived neurotrophic factor (BDNF), a key player in the pathophysiology of major depression and the action of antidepressants, in the dentate gyrus of the hippocampus. Leptin treatment increases, whereas deficiency of leptin or leptin receptors decreases, total Bdnf mRNA levels, with distinct expression profiles of specific exons, in the hippocampus. Epigenetic analyses reveal that histone modifications, but not DNA methylation, underlie exon-specific transcription of the Bdnf gene induced by leptin. This is mediated by stimulation of AKT signaling, which in turn activates histone acetyltransferase p300 (p300 HAT), leading to changes in histone H3 acetylation and methylation at specific Bdnf promoters. Furthermore, deletion of Bdnf in the dentate gyrus, or specifically in LepRb-expressing neurons, abolishes the antidepressant-like effects of leptin. These findings indicate that leptin, acting via an AKT-p300 HAT epigenetic cascade, induces exon-specific Bdnf expression, which in turn is indispensable for leptin-induced antidepressant-like effects.
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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 Socratic graph.