{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:38:17Z","timestamp":1791931097755,"version":"4.3.4"},"reference-count":53,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"vor","delay-in-days":269,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL101250"],"award-info":[{"award-number":["R01HL101250"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,10,1]]},"abstract":"<jats:p>Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity-associated molecular features that may contribute to obesity-related diseases. Using circulating monocytes from 1,264 Multi-Ethnic Study of Atherosclerosis (MESA) participants, we quantified the transcriptome and epigenome. We discovered that alterations in a network of coexpressed cholesterol metabolism genes are a signature feature of obesity and inflammatory stress. This network included 11 BMI-associated genes related to sterol uptake (\u2191LDLR, \u2193MYLIP), synthesis (\u2191SCD, FADS1, HMGCS1, FDFT1, SQLE, CYP51A1, SC4MOL), and efflux (\u2193ABCA1, ABCG1), producing a molecular profile expected to increase intracellular cholesterol. Importantly, these alterations were associated with T2D and coronary artery calcium (CAC), independent from cardiometabolic factors, including serum lipid profiles. This network mediated the associations between obesity and T2D\/CAC. Several genes in the network harbored C-phosphorus-G dinucleotides (e.g., ABCG1\/cg06500161), which overlapped Encyclopedia of DNA Elements (ENCODE)-annotated regulatory regions and had methylation profiles that mediated the associations between BMI\/inflammation and expression of their cognate genes. Taken together with several lines of previous experimental evidence, these data suggest that alterations of the cholesterol metabolism gene network represent a molecular link between obesity\/inflammation and T2D\/CAC.<\/jats:p>","DOI":"10.2337\/db14-1314","type":"journal-article","created":{"date-parts":[[2015,7,8]],"date-time":"2015-07-08T02:32:54Z","timestamp":1436322774000},"page":"3464-3474","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":96,"title":["Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease"],"prefix":"10.2337","volume":"64","author":[{"given":"Jingzhong","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay M.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Zeller","sequence":"additional","affiliation":[{"name":"University Heart Center Hamburg, Clinic for General and Interventional Cardiology, and DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"University Heart Center Hamburg, Clinic for General and Interventional Cardiology, and DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Lohman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.","family":"Nicklas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Kritchevsky","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqing","family":"Huang","sequence":"additional","affiliation":[{"name":"Duke University, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"Department of Biomathematics and Bioinformatics, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Soranzo","sequence":"additional","affiliation":[{"name":"CRS4 Bioinformatica, Pula, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Settlage","sequence":"additional","affiliation":[{"name":"Virginia Bioinformatics Institute at Virginia Tech, Blacksburg, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Chi","family":"Chuang","sequence":"additional","affiliation":[{"name":"Section on Molecular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark O.","family":"Goodarzi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.-D. 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