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This review provides a broad overview of the pathophysiological processes that from adipose tissue dysfunction leading to altered multi-tissue crosstalk relevant to regulating energy homeostasis and the etiology of obesity. First, a comprehensive description of the role of adipose tissue was reported. Then, attention was turned toward the unhealthy expansion of adipose tissue, low-grade inflammatory state, metabolic inflexibility, and mitochondrial dysfunction as root causes of systemic metabolic alterations. In addition, a short spot was devoted to iron deficiency in obese conditions and the role of the hepcidin\u2013ferroportin relationship in the management of this issue. Finally, different classes of bioactive food components were described with a perspective to enhance their potential preventive and therapeutic use against obesity-related diseases.<\/jats:p>","DOI":"10.3390\/antiox12061172","type":"journal-article","created":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T07:49:23Z","timestamp":1685346563000},"page":"1172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["From Obesity-Induced Low-Grade Inflammation to Lipotoxicity and Mitochondrial Dysfunction: Altered Multi-Crosstalk between Adipose Tissue and Metabolically Active Organs"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5890-1002","authenticated-orcid":false,"given":"Gina","family":"Cavaliere","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy"},{"name":"Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant\u2019Angelo, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5239-4329","authenticated-orcid":false,"given":"Fabiano","family":"Cimmino","sequence":"additional","affiliation":[{"name":"Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant\u2019Angelo, 80126 Naples, Italy"},{"name":"Department of Biology, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4096-6876","authenticated-orcid":false,"given":"Giovanna","family":"Trinchese","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Catapano","sequence":"additional","affiliation":[{"name":"Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant\u2019Angelo, 80126 Naples, Italy"},{"name":"Department of Biology, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Petrella","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Lucchin","sequence":"additional","affiliation":[{"name":"Dietetics and Clinical Nutrition, Bolzano Health District, 39100 Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pina","family":"Mollica","sequence":"additional","affiliation":[{"name":"Centro Servizi Metrologici e Tecnologici Avanzati (CeSMA), Complesso Universitario di Monte Sant\u2019Angelo, 80126 Naples, Italy"},{"name":"Department of Biology, University of Naples Federico II, 80126 Naples, Italy"},{"name":"Task Force on Microbiome Studies, University of Naples Federico II, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/s41591-022-02156-9","article-title":"Comorbidities, Multimorbidity and COVID-19","volume":"29","author":"Russell","year":"2023","journal-title":"Nat. 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