{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:00:24Z","timestamp":1782990024649,"version":"3.54.5"},"reference-count":127,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T00:00:00Z","timestamp":1652486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Cassa di Risparmio di Perugia \u201cSettore Ricerca Scientifica e Tecnologica 2019: Invecchiamento","award":["\u201c2019.0320\u201d and 20420 (2021.0339)"],"award-info":[{"award-number":["\u201c2019.0320\u201d and 20420 (2021.0339)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adipose tissue (AT) is a remarkably plastic and active organ with functional pleiotropism and high remodeling capacity. Although the expansion of fat mass, by definition, represents the hallmark of obesity, the dysregulation of the adipose organ emerges as the forefront of the link between adiposity and its associated metabolic and cardiovascular complications. The dysfunctional fat displays distinct biological signatures, which include enlarged fat cells, low-grade inflammation, impaired redox homeostasis, and cellular senescence. While these events are orchestrated in a cell-type, context-dependent and temporal manner, the failure of the adipose precursor cells to form new adipocytes appears to be the main instigator of the adipose dysregulation, which, ultimately, poses a deleterious milieu either by promoting ectopic lipid overspill in non-adipose targets (i.e., lipotoxicity) or by inducing an altered secretion of different adipose-derived hormones (i.e., adipokines and lipokines). This \u201cadipocentric view\u201d extends the previous \u201cexpandability hypothesis\u201d, which implies a reduced plasticity of the adipose organ at the nexus between unhealthy fat expansion and the development of obesity-associated comorbidities. In this review, we will briefly summarize the potential mechanisms by which adaptive changes to variations of energy balance may impair adipose plasticity and promote fat organ dysfunction. We will also highlight the conundrum with the perturbation of the adipose microenvironment and the development of cardio-metabolic complications by focusing on adipose lipoxidation, inflammation and cellular senescence as a novel triad orchestrating the conspiracy to adipose dysfunction. Finally, we discuss the scientific rationale for proposing adipose organ plasticity as a target to curb\/prevent adiposity-linked cardio-metabolic complications.<\/jats:p>","DOI":"10.3390\/ijms23105511","type":"journal-article","created":{"date-parts":[[2022,5,15]],"date-time":"2022-05-15T09:48:22Z","timestamp":1652608102000},"page":"5511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Adipose Tissue Plasticity in Response to Pathophysiological Cues: A Connecting Link between Obesity and Its Associated Comorbidities"],"prefix":"10.3390","volume":"23","author":[{"given":"Michelatonio","family":"De Fano","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Endocrinology and Metabolism, Azienda Ospedaliera Santa Maria Misericordia, Ospedale di Perugia, Piazzale Gambuli, 06081 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3849-757X","authenticated-orcid":false,"given":"Desir\u00e8e","family":"Bartolini","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Human Anatomy Laboratory, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Tortoioli","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrinology and Metabolism, Azienda Ospedaliera Santa Maria Misericordia, Ospedale di Perugia, Piazzale Gambuli, 06081 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Vermigli","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrinology and Metabolism, Azienda Ospedaliera Santa Maria Misericordia, Ospedale di Perugia, Piazzale Gambuli, 06081 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Malara","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrinology and Metabolism, Azienda Ospedaliera Santa Maria Misericordia, Ospedale di Perugia, Piazzale Gambuli, 06081 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3626-051X","authenticated-orcid":false,"given":"Francesco","family":"Galli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Human Anatomy Laboratory, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Murdolo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrinology and Metabolism, Azienda Ospedaliera Santa Maria Misericordia, Ospedale di Perugia, Piazzale Gambuli, 06081 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"GBD 2015 Obesity Collaborators, Afshin, A., Forouzanfar, M.H., Reitsma, M.B., Sur, P., Estep, K., Lee, A., Marczak, L., Mokdad, A.H., and Moradi-Lakeh, M. 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