{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:15:17Z","timestamp":1788322517224,"version":"build-2803163510"},"reference-count":41,"publisher":"American Diabetes Association","issue":"1","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:p>Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. We detail that mice lacking Reverb\u03b1 exhibit enhanced fat storage without the predicted increased WAT inflammation or loss of insulin sensitivity. In contrast to most animal models of obesity and obese human patients, Reverb\u03b1\u2212\/\u2212 mice exhibit elevated serum adiponectin levels and increased adiponectin secretion from WAT explants in vitro, highlighting a potential anti-inflammatory role of this adipokine in hypertrophic WAT. Indeed, adiponectin was found to suppress primary macrophage responses to lipopolysaccharide and proinflammatory fatty acids, and this suppression depended on glycogen synthase kinase 3\u03b2 activation and induction of A20. Attenuated inflammatory responses in Reverb\u03b1\u2212\/\u2212 WAT depots were associated with tonic elevation of A20 protein and ex vivo shown to depend on A20. We also demonstrate that adipose A20 expression in obese human subjects exhibits a negative correlation with measures of insulin sensitivity. Furthermore, bariatric surgery\u2013induced weight loss was accompanied by enhanced WAT A20 expression, which is positively correlated with increased serum adiponectin and improved metabolic and inflammatory markers, including C-reactive protein. The findings identify A20 as a mediator of adiponectin anti-inflammatory action in WAT and a potential target for mitigating obesity-related pathology.<\/jats:p>","DOI":"10.2337\/db13-1835","type":"journal-article","created":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T05:17:17Z","timestamp":1409894237000},"page":"128-136","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":41,"title":["Adiponectin Induces A20 Expression in Adipose Tissue to Confer Metabolic Benefit"],"prefix":"10.2337","volume":"64","author":[{"given":"Laura E.","family":"Hand","sequence":"first","affiliation":[{"name":"Faculty of Life Sciences, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Usan","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth J.S.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, University of Manchester, Manchester, U.K."},{"name":"School of Biological Sciences, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance Y.","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil","family":"Ammori","sequence":"additional","affiliation":[{"name":"Centre for Advanced Discovery and Experimental Therapeutics, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Aghamohammadzadeh","sequence":"additional","affiliation":[{"name":"Centre for Advanced Discovery and Experimental Therapeutics, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Handrean","family":"Soran","sequence":"additional","affiliation":[{"name":"Centre for Advanced Discovery and Experimental Therapeutics, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Greenstein","sequence":"additional","affiliation":[{"name":"Centre for Advanced Discovery and Experimental Therapeutics, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.I.","family":"Loudon","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bechtold","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Ray","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2014,9,4]]},"reference":[{"key":"2022031223033689300_B1"},{"key":"2022031223033689300_B2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.it.2011.04.008","article-title":"Defining macrophage phenotype and function in adipose tissue","volume":"32","author":"Dalmas","year":"2011","journal-title":"Trends Immunol"},{"key":"2022031223033689300_B3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1126\/science.7678183","article-title":"Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance","volume":"259","author":"Hotamisligil","year":"1993","journal-title":"Science"},{"key":"2022031223033689300_B4","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1172\/JCI117899","article-title":"The expression of tumor necrosis factor in human adipose tissue. 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