{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:59:32Z","timestamp":1785473972312,"version":"3.56.0"},"reference-count":324,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universit\u00e0 Telematica San Raffaele","award":["(FIN\/RIC) 2023"],"award-info":[{"award-number":["(FIN\/RIC) 2023"]}]},{"award":["(FIN\/RIC) 2023"],"award-info":[{"award-number":["(FIN\/RIC) 2023"]}],"id":[{"id":"https:\/\/ror.org\/02rwycx38","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Obesity is a multifactorial condition characterized by profound metabolic and inflammatory dysregulation that alters the adipose tissue-central nervous system (CNS) relationship. This paper critically summarizes the biochemical and cellular mechanisms governing this bidirectional crosstalk, moving beyond a descriptive perspective to propose an integrated model of peripheral-central interaction. White adipose tissue (WAT) and brown adipose tissue (BAT), modulated by the sympathetic nervous system (SNS), communicate with hypothalamic circuits (POMC and AgRP neurons) both through traditional endocrine signals (leptin, adiponectin, resistin, apelin) and through lipid mediators and extracellular vesicles (EVs) capable of crossing the blood\u2013brain barrier (BBB). Under conditions of nutritional excess, the accumulation of lipotoxic lipid species (such as palmitate and ceramides) and the inflammatory polarization of brain macrophages (M1\/BAMs) induce mitochondrial stress and central resistance to leptin and insulin, altering the adiposity set point. In parallel, we review emerging nutritional strategies based on polyunsaturated fatty acids (PUFAs), polyphenols, and short-chain fatty acids (SCFAs), and critically evaluate innovative technological platforms (nanoencapsulation, precision fermentation, and 3D food printing) designed to optimize nutrient bioaccessibility and restore adipose-CNS axis homeostasis, discussing current challenges for clinical translation.<\/jats:p>","DOI":"10.3390\/metabo16080533","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:13:47Z","timestamp":1785320027000},"page":"533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adipose Tissue\u2013Central Nervous System Axis in Obesity: Molecular Mechanisms, Inflammation, and Nutritional and Technological Implications"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5857-8049","authenticated-orcid":false,"given":"Serena","family":"Castelli","sequence":"first","affiliation":[{"name":"Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Rome, Via di Val Cannuta, 247, 00166 Rome, Italy"},{"name":"IRCCS San Raffaele Roma, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4327-0521","authenticated-orcid":false,"given":"Gilda","family":"Aiello","sequence":"additional","affiliation":[{"name":"Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Rome, Via di Val Cannuta, 247, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5801-0752","authenticated-orcid":false,"given":"Alessandra","family":"De Bruno","sequence":"additional","affiliation":[{"name":"Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Rome, Via di Val Cannuta, 247, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4835-0571","authenticated-orcid":false,"given":"Deborah","family":"Fratantonio","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, LUM University, S.S. 100 Km 18, 70100 Casamassima, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9079-0047","authenticated-orcid":false,"given":"Gianluca","family":"Tripodi","sequence":"additional","affiliation":[{"name":"Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Rome, Via di Val Cannuta, 247, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5646-4325","authenticated-orcid":false,"given":"Vincenzo","family":"Aiello","sequence":"additional","affiliation":[{"name":"Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Rome, Via di Val Cannuta, 247, 00166 Rome, Italy"},{"name":"IRCCS San Raffaele Roma, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7509-5487","authenticated-orcid":false,"given":"Mauro","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Rome, Via di Val Cannuta, 247, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7003-3172","authenticated-orcid":false,"given":"Sara","family":"Baldelli","sequence":"additional","affiliation":[{"name":"Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Rome, Via di Val Cannuta, 247, 00166 Rome, Italy"},{"name":"IRCCS San Raffaele Roma, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hahm, J.R., Jo, M.H., Ullah, R., Kim, M.W., and Kim, M.O. 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