ArticleDiabetologia2014
Leptin resistance and obesity in mice with deletion of methyl-CpG-binding protein 2 (MeCP2) in hypothalamic pro-opiomelanocortin (POMC) neurons.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Endocrine disorders in Rett syndrome: a systematic review of the literature.Frontiers in endocrinology · 2024Pooled it
- Spatially resolved mapping of histones reveals selective neuronal response in Rett syndrome.The FEBS journal · 2026Article
- Pubertal development and hypothalamic-pituitary-gonadal axis are altered in male mice lacking Mecp2.Journal of neuroendocrinology · 2026Article
- MeCP2 dysregulation inhibits mitophagy and impairs neural development in cortical organoids.Journal of advanced research · 2026Article
- Leptin antagonism improves Rett syndrome phenotype in symptomatic Mecp2-deficient mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Neuronal Plasticity-Dependent Paradigm and Young Plasma Treatment Prevent Synaptic and Motor Deficit in a Rett Syndrome Mouse Model.Biomolecules · 2025Article
- Epigenetic Mechanisms of Obesity: Insights from Transgenic Animal Models.Life (Basel, Switzerland) · 2025Review
- POMC-specific knockdown of MeCP2 leads to adverse phenotypes in mice chronically exposed to high fat diet.Behavioural brain research · 2024Article
- Prevalence of Endocrinopathies in a Cohort of Patients with Rett Syndrome: A Two-Center Observational Study.Genes · 2024Observational
- The Mechanism of Leptin Resistance in Obesity and Therapeutic Perspective.Advances in experimental medicine and biology · 2024Review
- DNA Methylation in the Hypothalamic Feeding Center and Obesity.Journal of obesity & metabolic syndrome · 2023Review
- Hypothalamic DNA 5-hydroxymethylation levels are altered by diet-induced weight gain during the development of obesity in a sex-specific manner.Brain research · 2023Article
- Article
- Leptin signaling and leptin resistance.Medical review (2021) · 2022Review
- Sex and Exposure to Postnatal Chlorpyrifos Influence the Epigenetics of Feeding-Related Genes in a TransgenicInternational journal of environmental research and public health · 2020Article
- Sirtuin (SIRT)-1: At the crossroads of puberty and metabolism.Current opinion in endocrine and metabolic research · 2020Article
- Article
- Diet-induced DNA methylation within the hypothalamic arcuate nucleus and dysregulated leptin and insulin signaling in the pathophysiology of obesity.Food science & nutrition · 2019Review
- The role of epigenetics in hypothalamic energy balance control: implications for obesity.Cell stress · 2019Review
- High-fat diet accelerates extreme obesity with hyperphagia in female heterozygous Mecp2-null mice.PloS one · 2019Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
Abstract
aims/hypothesisPro-opiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) regulate energy homeostasis by secreting α-melanocyte-stimulating hormone (α-MSH), derived from POMC precursor, in response to leptin signalling. Expression of Pomc is subject to multiple modes of regulation, including epigenetic regulation. Methyl-CpG-binding protein 2 (MeCP2), a nuclear protein essential for neuronal function, interacts with promoters to influence gene expression. We aim to address whether MeCP2 regulates hypothalamic Pomc expression and to investigate the role of epigenetics, particularly DNA methylation, in this process.
methodsWe generated a mouse line with MeCP2 specifically deleted in POMC neurons (Mecp2 flox/y /Pomc-Cre [PKO]) and characterised its metabolic phenotypes. We examined the DNA methylation pattern of the Pomc promoter and its impact on hypothalamic gene expression. We also studied the requirement of MeCP2 for, and the effects of, DNA methylation on Pomc promoter activity using luciferase assays.
resultsPKO mice are overweight, with increased fat mass resulting from increased food intake and respiratory exchange ratio. PKO mice also exhibit elevated plasma leptin. Deletion of MeCP2 in POMC neurons leads to increased DNA methylation of the hypothalamic Pomc promoter and reduced Pomc expression. Furthermore, in vitro studies show that hypermethylation of the Pomc promoter reduces its transcriptional activity and reveal a functional synergy between MeCP2 and cAMP responsive element binding protein 1 (CREB1) in positively regulating the Pomc promoter. CONCLUSIONS/
interpretationOur results demonstrate that MeCP2 positively regulates Pomc expression in the hypothalamus. Absence of MeCP2 in POMC neurons leads to increased DNA methylation of the Pomc promoter, which, in turn, downregulates Pomc expression, leading to obesity in mice with an accentuating degree of leptin resistance.
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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.