REVIEW article
Front. Endocrinol.
Sec. Neuroendocrine Science
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1645474
Epigenetic Modification of Hypothalamic Neuropeptides and Receptors: A Key to Understanding Metabolic Dysfunction
Provisionally accepted
- College of Health Solutions, Arizona State University, Tempe, United States
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The hypothalamus plays a central role in regulating metabolism by integrating neuropeptide signaling with environmental cues to maintain energy homeostasis. Adverse environmental factors, such as obesogenic diet, undernutrition, stress, and sedentary lifestyles, can disrupt the normal regulation of key hypothalamic neuropeptides and metabolic hormone receptors through epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA regulation. These epigenetic alterations are not merely transient; they can be heritable and may influence metabolic health across generations, highlighting the critical need to understand the underlying epigenetic mechanisms. In this review, we provide a comprehensive overview of how environmental factors shape the epigenetic landscape of hypothalamic neuropeptides (pre-opiomelanocortin, neuropeptide Y, and agouti-related peptide) and metabolic hormone receptors (leptin receptor and insulin receptor), thereby modulating their expression and contributing to long-term metabolic outcomes. A better understanding of environment-epigenome interactions holds promise for the development of innovative therapeutic strategies to combat obesity and metabolic disorders.
Keywords: Hypothalamus, epigenetics, Neuropeptides, Metabolism, Obesity, Hormone receptors
Received: 11 Jun 2025; Accepted: 21 Aug 2025.
Copyright: © 2025 Oladun, Mall and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Min-Hyun Kim, College of Health Solutions, Arizona State University, Tempe, United States
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