{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T02:48:37Z","timestamp":1776048517758,"version":"3.50.1"},"reference-count":66,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82150002"],"award-info":[{"award-number":["82150002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070438"],"award-info":[{"award-number":["82070438"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20220711"],"award-info":[{"award-number":["BK20220711"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity Reviews"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity is a well\u2010documented cardiovascular risk factor. Here, we sought to investigate whether obesity causes subclinical cardiac remodeling and heart failure (HF), and if so, to perform a systematic scan of the plasma protein for novel drug targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We leveraged visceral adipose tissue (VAT), waist circumference (WC), and waist\u2010to\u2010hip ratio (WHR)\u2014all adjusted for body mass index (BMI)\u2014as indicators of obesity. Two\u2010sample Mendelian randomization (MR) analyses were used to estimate the independent, causal effects of obesity on cardiovascular magnetic resonance (CMR)\u2013derived cardiac traits and HF risk. Mediation analyses followed by druggability assessment were conducted to identify promising protein targets for therapeutic translation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genetically determined VATadjBMI, WCadjBMI, and WHRadjBMI presented broad causal associations with alterations of distinct cardiac phenotypes, most of which remained significant after controlling for obesity\u2013induced cardiometabolic risk factors, including hypertension, type 2 diabetes, and adverse lipid profiles. By contrast, WHRadjBMI is the only independent causal predictor for HF risk. Of 142 proteins with mediating effects, scavenger receptor class A member 5 (SCARA5), membrane cofactor protein (CD46), and alpha\u20101\u2010antichymotrypsin (SERPINA3) may contribute to the early\u2010stage adverse cardiovascular effect of obesity, whereas apolipoprotein C\u2010III (APOC3), mitochondrial aldehyde dehydrogenase 2 (ALDH2), and chordin\u2010like protein 2 (CHRDL2) may further promote the development of obesity\u2013driven HF. Medications targeted at these candidate proteins are either approved or under evaluation in clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our MR findings provided genetic evidence for the direct, causal associations of obesity with cardiac remodeling and HF, while also outlining druggable proteins as promising therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/obr.70059","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T03:37:46Z","timestamp":1765597066000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Circulating Proteins Link Obesity With Cardiac Remodeling: Insights From Mendelian Randomization"],"prefix":"10.1111","volume":"27","author":[{"given":"Yukang","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital with Nanjing Medical University  Nanjing China"},{"name":"Department of Cardiology, The Affiliated Suzhou Hospital with Nanjing Medical University Suzhou Municipal Hospital, Gusu School, Nanjing Medical University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuer","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0365-2103","authenticated-orcid":false,"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0833-0445","authenticated-orcid":false,"given":"Wei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangqing","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital with Nanjing Medical University  Nanjing China"},{"name":"Department of Cardiology, The Affiliated Suzhou Hospital with Nanjing Medical University Suzhou Municipal 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