{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:07:33Z","timestamp":1784732853192,"version":"3.55.0"},"reference-count":27,"publisher":"American Physiological Society","issue":"8","funder":[{"DOI":"10.13039\/501100021778","name":"Agencia Nacional de Promoci\u00f3n de la Investigaci\u00f3n, el Desarrollo Tecnol\u00f3gico y la Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PICT 2020 Serie A 4000"],"award-info":[{"award-number":["PICT 2020 Serie A 4000"]}],"id":[{"id":"10.13039\/501100021778","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020302","name":"UNCUYO | Secretar\u00eda de Investigaci\u00f3n, Internacionales y Posgrado, Universidad Nacional de Cuyo","doi-asserted-by":"publisher","award":["SIIP 2022-2025"],"award-info":[{"award-number":["SIIP 2022-2025"]}],"id":[{"id":"10.13039\/501100020302","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:p>Obesity arises from the complex interplay between genetic and epigenetic factors, with developmental programming shaping adipose fate, energy homeostasis, and treatment responses later in life. Findings from the developmental origins of health and disease framework reveal that prenatal factors\u2014such as maternal nutrition, adiposity, hyperglycemia, smoking, and stress\u2014and early exposures imprint dynamic epigenetic marks\u2014DNA methylation, histone modifications, and noncoding RNAs\u2014on key tissues (adipose and hypothalamic circuits), which are associated with both childhood and adult adiposity. These marks contribute to an \u201cepigenetic memory\u201d that exhibits a graded decay model rather than absolute permanence yet persists even after weight loss, limiting full reversibility of the obese phenotype. This phenomenon is supported by transcriptional and epigenomic profiles of human and mouse adipose tissue following weight loss. In obesity, adipose niche remodeling involves chronic inflammation, fibrosis, and macrophage-fibroblast interactions within \u201ccrown-like\u201d structures, with oncostatin M-macrophage-inducible C-type lectin circuits modulating fibrosis. In prevention and therapy, combining lifestyle interventions with dual- or selective-incretin-based drugs results in significant weight loss and improves body composition and muscle function. Beyond classical metabolic targets, several antiobesity drugs\u2014including metformin, thiazolidinediones, glucagon-like peptide 1 agonists, SGLT2 inhibitors, and nutraceuticals such as resveratrol\u2014also exert epigenetic remodeling effects in liver, muscle, and adipose tissue, although clinical evidence for some nutraceuticals remains limited by bioavailability. Integrating epigenetic biomarkers with critical developmental windows, together with digital health and personalized medicine, could optimize risk stratification and refine our understanding of obesity as a modifiable, yet path-dependent biological condition.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00032.2026","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T17:01:37Z","timestamp":1781542897000},"page":"347-354","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Obesity as an epigenetic continuum: developmental roots, adipose remodeling, and the limits of reversibility"],"prefix":"10.1152","volume":"58","author":[{"given":"Le\u00f3n","family":"Ferder","sequence":"first","affiliation":[{"name":"Ponce Health Sciences University","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n","family":"Garc\u00eda 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