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Epigenetic mechanisms control cellular morphology and function. Such regulatory mechanisms involve histone modifications, chromatin remodeling, DNA methylation, non-coding regulatory RNA molecules, and RNA modifications. One of the most well-studied epigenetic modifications is DNA methylation that plays key roles in development, health, and disease. Our brain is probably the most complex part of our body, with a high level of DNA methylation. A key protein that binds to different types of methylated DNA in the brain is the methyl-CpG binding protein 2 (MeCP2). MeCP2 acts in a dose-dependent manner and its abnormally high or low expression level, deregulation, and\/or genetic mutations lead to neurodevelopmental disorders and aberrant brain function. Recently, some of MeCP2-associated neurodevelopmental disorders have emerged as neurometabolic disorders, suggesting a role for MeCP2 in brain metabolism. Of note, MECP2 loss-of-function mutation in Rett Syndrome is reported to cause impairment of glucose and cholesterol metabolism in human patients and\/or mouse models of disease. The purpose of this review is to outline the metabolic abnormalities in MeCP2-associated neurodevelopmental disorders that currently have no available cure. We aim to provide an updated overview into the role of metabolic defects associated with MeCP2-mediated cellular function for consideration of future therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms24044218","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T05:27:01Z","timestamp":1676870821000},"page":"4218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["MeCP2 Is an Epigenetic Factor That Links DNA Methylation with Brain Metabolism"],"prefix":"10.3390","volume":"24","author":[{"given":"Yen My","family":"Vuu","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris-Tiann","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-6116","authenticated-orcid":false,"given":"Mojgan","family":"Rastegar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"key":"ref_1","first-page":"57","article-title":"Chromatin Structure and Epigenetics","volume":"Volume 13","author":"Urbano","year":"2015","journal-title":"Advances in Genetics Research"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/jcp.21678","article-title":"Epigenetic control","volume":"219","author":"Delcuve","year":"2009","journal-title":"J. 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