{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:00:02Z","timestamp":1790161202723,"version":"4.1.0"},"reference-count":180,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity Reviews"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The distribution of adipose tissue is a key determinant of obesity\u2010related disease risk. When the capacity of subcutaneous adipose tissue to safely store energy is exceeded, lipid overflow into visceral depots occurs, increasing free fatty acid flux, promoting insulin resistance, and triggering chronic low\u2010grade inflammation. More than 80\u2009years ago, the physician Jean Vague recognized the association between android (central) obesity and cardiometabolic disease; subsequent advances from imaging technologies have expanded this framework to include ectopic fat accumulation within non\u2010adipose organs. Ectopic fat deposition in the liver, pancreas, heart, kidneys, skeletal muscle, and upper airway contributes to organ\u2010specific dysfunction through mechanisms including lipotoxicity, adipokine dysregulation, oxidative stress, and local inflammatory signaling. This review summarizes the evidence linking visceral and ectopic fat to metabolic dysfunction\u2013associated steatotic liver disease and steatohepatitis, type 2 diabetes, cardiovascular and renal disease, sarcopenic obesity, and obstructive sleep apnea. Importantly, visceral and ectopic fat depots are modifiable. Lifestyle\u2010induced energy deficit, incretin\u2010based pharmacotherapy, and metabolic bariatric surgery reduce visceral and ectopic fat and improve glycemic control, liver fat content, cardiovascular risk factors, physical function, and sleep\u2010disordered breathing. Incorporating ectopic fat characterization into clinical practice may enhance risk stratification and support more personalized management of obesity phenotypes.<\/jats:p>","DOI":"10.1111\/obr.70229","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:59:10Z","timestamp":1790157550000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Eighty Years After Vague: Advances in Understanding Ectopic Fat and Metabolic Dysfunction"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7066-5292","authenticated-orcid":false,"given":"Caterina","family":"Conte","sequence":"first","affiliation":[{"name":"San Raffaele Roma University  Rome Italy"},{"name":"IRCCS MultiMedica  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9576-1050","authenticated-orcid":false,"given":"Priya","family":"Sumithran","sequence":"additional","affiliation":[{"name":"School of Translational Medicine Monash University  Melbourne Victoria Australia"},{"name":"Department of Endocrinology and Diabetes Bayside Health (Alfred Care Group)  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5521-5445","authenticated-orcid":false,"given":"Carel W.","family":"le Roux","sequence":"additional","affiliation":[{"name":"University College Dublin  Dublin Ireland"},{"name":"Ulster University  Coleraine UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3830-3173","authenticated-orcid":false,"given":"Alexander Dimitri","family":"Miras","sequence":"additional","affiliation":[{"name":"School of Medicine Ulster University  Derry UK"},{"name":"Department of Metabolism, Digestion and Reproduction Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Van Gaal","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Metabolism Antwerp University Hospital  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"e_1_2_13_2_1","first-page":"339","article-title":"Sexual Differentiation; Factor Determining Forms of Obesity","volume":"55","author":"Vague J.","year":"1947","journal-title":"Presse M\u00e9dicale (1893)"},{"key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/ajcn\/4.1.20","article-title":"The Degree of Masculine Differentiation of Obesities: A Factor Determining Predisposition to Diabetes, Atherosclerosis, Gout, and Uric Calculous Disease","volume":"4","author":"Vague J.","year":"1956","journal-title":"American Journal of Clinical Nutrition"},{"key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1161\/CIR.0b013e318233bc6a","article-title":"Assessing Adiposity: A Scientific Statement From the American Heart Association","volume":"124","author":"Cornier M. 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