{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T01:36:36Z","timestamp":1784943396280,"version":"3.55.0"},"reference-count":227,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad UTE."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity is increasingly recognized not only as a metabolic disorder, but also as a state of chronic low-grade inflammation that predisposes to systemic complications. Within this context, Dercum\u2019s disease (DD), or adiposis dolorosa, emerges as a rare yet debilitating disorder characterized by painful subcutaneous lipomas, most commonly affecting middle-aged women. Despite its clinical impact, DD remains underdiagnosed and is often misclassified as lipedema, fibromyalgia, or lipomatosis, complicating prevalence estimates and hindering the development of targeted interventions. Current evidence suggests that DD represents a distinctive model of inflammatory obesity, where adipose tissue actively contributes to pain generation rather than serving as a passive fat reservoir. Histological and molecular findings point to adipose tissue dysfunction, immune cell infiltration, and elevated secretion of pro-inflammatory adipokines, signals which appear to fuel systemic low-grade inflammation, perineural immune interactions, and nociceptor sensitization. Peripheral mechanisms further shape the clinical phenotype. While familial clustering suggests possible genetic contributions, no definitive markers have been identified, and the role of obesity-induced epigenetic modifications remains unexplored. Therapeutic strategies remain largely symptomatic, including analgesics, antidepressants, physical rehabilitation, and surgical excision of lipomas, whereas molecularly targeted and diet-based interventions are still experimental. This article discusses the pathophysiology of DD, current treatments, and future perspectives, emphasizing that advancing patient registries, omics-based analyses, and interdisciplinary clinical trials will be crucial to elucidate disease mechanisms and guide novel therapies. Improved understanding of DD may not only enhance patient care, but also provide broader insights into the interplay between obesity, inflammation, and chronic pain.<\/jats:p>","DOI":"10.3390\/ijms262211130","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T09:58:42Z","timestamp":1763459922000},"page":"11130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Molecular Mechanisms Underlying Dercum\u2019s Disease: Exploring the Intersection of Obesity, Pain, and Inflammation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4234-5524","authenticated-orcid":false,"given":"Claudia","family":"Reytor-Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n en Salud P\u00fablica y Epidemiolog\u00eda Cl\u00ednica (CISPEC), Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito 170527, Ecuador"},{"name":"Escuela de Medicina, Pontificia Universidad Cat\u00f3lica del Ecuador, Santo Domingo 230203, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9670-6376","authenticated-orcid":false,"given":"Emilia","family":"Jim\u00e9nez-Flores","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Salud P\u00fablica y Epidemiolog\u00eda Cl\u00ednica (CISPEC), Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito 170527, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6194-4047","authenticated-orcid":false,"given":"Melannie","family":"Toral-Noristz","sequence":"additional","affiliation":[{"name":"Escuela de Medicina, Universidad Esp\u00edritu Santo, Samborond\u00f3n 0901952, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5317-8548","authenticated-orcid":false,"given":"Mart\u00edn","family":"Campuzano-Donoso","sequence":"additional","affiliation":[{"name":"Independent Researcher, Quito 170102, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6417-5550","authenticated-orcid":false,"given":"N\u00e1thaly Mercedes","family":"Rom\u00e1n-Galeano","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Salud P\u00fablica y Epidemiolog\u00eda Cl\u00ednica (CISPEC), Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito 170527, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3641-1501","authenticated-orcid":false,"given":"Daniel","family":"Simancas-Racines","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Salud P\u00fablica y Epidemiolog\u00eda Cl\u00ednica (CISPEC), Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito 170527, Ecuador"},{"name":"Facultad de Salud y Bienestar, Pontificia Universidad Cat\u00f3lica del Ecuador, Quito 170143, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1001\/jama.2016.6458","article-title":"Trends in Obesity Among Adults in the United States, 2005 to 2014","volume":"315","author":"Flegal","year":"2016","journal-title":"J. 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