{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:53:49Z","timestamp":1791244429538,"version":"4.1.0"},"reference-count":33,"publisher":"Georg Thieme Verlag KG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diet-induced obesity is increasingly understood as a disorder of central\n                    regulatory failure rather than simple energy imbalance. Two\n                    mechanisms\u2014impaired hypothalamic autophagy and epigenetic reprogramming\n                    of feeding-regulatory genes\u2014have been independently implicated in\n                    perpetuating obesity, yet their mechanistic intersection remains poorly defined.\n                    This perspective proposes that these processes are not parallel phenomena but\n                    components of a single self-reinforcing autophagy\u2013epigenome axis\n                    (presented here as a working hypothesis) governed by shared nutrient-sensing\n                    hubs (mechanistic target of rapamycin complex 1, AMP-activated protein kinase,\n                    and sirtuin 1). In this model, chronic caloric excess simultaneously suppresses\n                    autophagic flux and induces epigenetic silencing of autophagy regulators,\n                    potentially creating a feed-forward loop that locks hypothalamic neurons into a\n                    pro-inflammatory, orexigenic state resistant to dietary normalization. The\n                    frequent weight regain observed after glucagon-like peptide-1 receptor agonist\n                    discontinuation\u2014despite these agents\u2019 demonstrated capacity to\n                    enhance central autophagy and suppress neuroinflammation\u2014raises the\n                    possibility that current pharmacotherapies may suppress downstream consequences\n                    without erasing the underlying epigenetic code. This perspective synthesizes\n                    preclinical and emerging translational evidence to argue that durable obesity\n                    treatment will require interventions capable of simultaneously restoring\n                    autophagic flux and reversing epigenetic modifications within hypothalamic\n                    feeding circuits, and identifies critical knowledge gaps that must be addressed\n                    to advance this paradigm from a bench to a bedside.<\/jats:p>","DOI":"10.1055\/a-2961-3522","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:05:16Z","timestamp":1791241516000},"source":"Crossref","is-referenced-by-count":0,"title":["The Autophagy\u2013Epigenome Axis in Hypothalamic Neurons: A\n                    Unified Framework for Understanding Obesity Persistence and Therapeutic\n                    Resistance"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-1037","authenticated-orcid":false,"given":"Amin Roshdy","family":"Soliman","sequence":"additional","affiliation":[{"name":"Cairo University, Egypt","place":["Cairo"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S2213-8587(24)00283-3","article-title":"Hypothalamic obesity: from basic mechanisms to clinical perspectives","volume":"13","author":"J Argente","year":"2025","journal-title":"Lancet Diabetes Endocrinol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"e12598","DOI":"10.1111\/jne.12598","article-title":"Cell and molecular mechanisms behind diet-induced hypothalamic inflammation and\n                    obesity","volume":"30","author":"Y 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