{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:40:55Z","timestamp":1770288055390,"version":"3.49.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>The aim of this study was to unravel mechanisms whereby deficiency of the transcription factor Id3 (inhibitor of differentiation 3) leads to metabolic dysfunction in visceral obesity. We investigated the impact of loss of Id3 on hyaluronic acid (HA) production by the 3 HAS isoenzymes (HA synthases; -1, -2, and -3) and on obesity-induced adipose tissue (AT) accumulation of proinflammatory B cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>\n              Male\n              <jats:italic>Id3<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice and respective wild-type littermate controls were fed a 60% high-fat diet for 4 weeks. An increase in inflammatory B2 cells was detected in\n              <jats:italic>Id3<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              epididymal AT. HA accumulated in epididymal AT of high-fat diet\u2013fed\n              <jats:italic>Id3<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice and circulating levels of HA were elevated.\n              <jats:italic>Has2<\/jats:italic>\n              mRNA expression was increased in epididymal AT of\n              <jats:italic>Id3<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. Luciferase promoter assays showed that Id3 suppressed\n              <jats:italic>Has2<\/jats:italic>\n              promoter activity, while loss of\n              <jats:italic>Id3<\/jats:italic>\n              stimulated\n              <jats:italic>Has2<\/jats:italic>\n              promoter activity. Functionally, HA strongly promoted B2 cell adhesion in the AT and on cultured vascular smooth muscle cells of\n              <jats:italic>Id3<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, an effect sensitive to hyaluronidase.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              Our data demonstrate that loss of\n              <jats:italic>Id3<\/jats:italic>\n              increases\n              <jats:italic>Has2<\/jats:italic>\n              expression in the epididymal AT, thereby promoting HA accumulation. In turn, elevated HA content promotes HA-dependent binding of B2 cells and an increase in the B2 cells in the AT, which contributes to AT inflammation.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.120.315588","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T10:00:29Z","timestamp":1609408829000},"page":"796-807","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Helix-Loop-Helix Factor Id3 (Inhibitor of Differentiation 3)"],"prefix":"10.1161","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0239-3744","authenticated-orcid":true,"given":"Angelina","family":"Misiou","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacology, Medical Faculty, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, Germany (A.M., J.W.F., M.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-8617","authenticated-orcid":true,"given":"James C.","family":"Garmey","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center (J.C.G., J.M.H., D.B.H., V.O., C.M., M.A.M., C.A.M.), University of Virginia, Charlottesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack M.","family":"Hensien","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center (J.C.G., J.M.H., D.B.H., V.O., C.M., M.A.M., C.A.M.), University of Virginia, Charlottesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel B.","family":"Harmon","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center (J.C.G., J.M.H., D.B.H., V.O., C.M., M.A.M., C.A.M.), University of Virginia, Charlottesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8969-8454","authenticated-orcid":true,"given":"Victoria","family":"Osinski","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center (J.C.G., J.M.H., D.B.H., V.O., C.M., M.A.M., C.A.M.), University of Virginia, Charlottesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantel","family":"McSkimming","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center (J.C.G., J.M.H., D.B.H., V.O., C.M., M.A.M., C.A.M.), University of Virginia, Charlottesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6402-5942","authenticated-orcid":true,"given":"Melissa A.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center (J.C.G., J.M.H., D.B.H., V.O., C.M., M.A.M., C.A.M.), University of Virginia, Charlottesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens W.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacology, Medical Faculty, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, Germany (A.M., J.W.F., M.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4382-1947","authenticated-orcid":true,"given":"Maria","family":"Grandoch","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacology, Medical Faculty, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, Germany (A.M., J.W.F., M.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0049-9986","authenticated-orcid":true,"given":"Coleen A.","family":"McNamara","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center (J.C.G., J.M.H., D.B.H., V.O., C.M., M.A.M., C.A.M.), University of Virginia, Charlottesville."},{"name":"Division of Cardiovascular Medicine, Department of Medicine (C.A.M.), University of Virginia, 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