{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:11:54Z","timestamp":1791263514312,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2013,11,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Obesity can cause structural and functional abnormalities of the heart via complex but largely undefined mechanisms. Emerging evidence has shown that obesity results in reduced oxygen concentrations, or hypoxia, in adipose tissue. We hypothesized that the adipocyte hypoxia\u2010signaling pathway plays an essential role in the development of obesity\u2010associated cardiomyopathy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Using a mouse model in which the hypoxia\u2010inducible factor (\n              <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\n              ) pathway is activated by deletion of the von Hippel\u2013Lindau gene specifically in adipocytes, we found that mice with adipocyte\u2013von Hippel\u2013Lindau deletion developed lethal cardiac hypertrophy.\n              <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\n              activation in adipocytes results in overexpression of key cardiomyopathy\u2010associated genes in adipose tissue, increased serum levels of several proinflammatory cytokines including interleukin\u20101\u03b2 and monocyte chemotactic protein\u20101, and activation of nuclear factor\u2013\u03baB and nuclear factor of activated T cells in the heart. Interestingly, genetic deletion of\n              <jats:styled-content style=\"fixed-case\">\n                <jats:styled-content style=\"italic-in-any-context\">Hif2a<\/jats:styled-content>\n              <\/jats:styled-content>\n              , but not\n              <jats:styled-content style=\"fixed-case\">\n                <jats:styled-content style=\"italic-in-any-context\">Hif1a<\/jats:styled-content>\n              <\/jats:styled-content>\n              , was able to rescue cardiac hypertrophy and abrogate adipose inflammation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We have discovered a previously uncharacterized mechanism underlying a critical and direct role of the adipocyte\n              <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\n              \u20102 transcription factor in the development of adipose inflammation and pathological cardiac hypertrophy.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.113.000548","type":"journal-article","created":{"date-parts":[[2013,12,11]],"date-time":"2013-12-11T01:58:05Z","timestamp":1386727085000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":46,"title":["Activation of Hypoxia\u2010Inducible Factor\u20102 in Adipocytes Results in Pathological Cardiac Hypertrophy"],"prefix":"10.1161","volume":"2","author":[{"given":"Qun","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen 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