WeightNameValue
1000 Titel
  • Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease
1000 Autor/in
  1. Ding, Jingzhong |
  2. Reynolds, Lindsay M. |
  3. Zeller, Tanja |
  4. Müller, Christian |
  5. Lohman, Kurt |
  6. Nicklas, Barbara J. |
  7. Kritchevsky, Stephen B. |
  8. Huang, Zhiqing |
  9. de la Fuente, Alberto |
  10. Soranzo, Nicola |
  11. Settlage, Robert E. |
  12. Chuang, Chia-Chi |
  13. Howard, Timothy |
  14. Xu, Ning |
  15. Goodarzi, Mark O. |
  16. Chen, Y.-D. Ida |
  17. Rotter, Jerome I. |
  18. Siscovick, David S. |
  19. Parks, John S. |
  20. Murphy, Susan |
  21. Jacobs, David R. |
  22. Post, Wendy |
  23. Tracy, Russell P. |
  24. Wild, Philipp S. |
  25. Blankenberg, Stefan |
  26. Hoeschele, Ina |
  27. Herrington, David |
  28. McCall, Charles E. |
  29. Liu, Yongmei |
1000 Erscheinungsjahr 2015
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2015-07-07
1000 Erschienen in
1000 Quellenangabe
  • 64(10): 3464-3474
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587646/ |
  • https://doi.org/10.2337/db14-1314 |
1000 Ergänzendes Material
  • http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db14-1314/-/DC1 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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 (↑LDLR, ↓MYLIP), synthesis (↑SCD, FADS1, HMGCS1, FDFT1, SQLE, CYP51A1, SC4MOL), and efflux (↓ABCA1, 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.
1000 Fachgruppe
  1. Medizin |
  2. Biologie |
  3. Gesundheitswesen |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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1000 Label
1000 Förderer
  1. National Institutes of Health (NIH)
  2. Wake Forest University Claude D. Pepper Older Americans Independence Center
  3. National Heart, Lung, and Blood Institute
  4. National Center for Research Resources
1000 Fördernummer
  1. R01-HL-101250; R01-HL-093713
  2. P30-AG21332
  3. N01-HC-95159; N01-HC-95165; N01-HC-95169
  4. UL1-RR-024156; UL1-RR-025005
1000 Förderprogramm
  1. -
  2. -
  3. -
  4. -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6410737.rdf
1000 Erstellt am 2018-10-23T12:53:37.041+0200
1000 Erstellt von 122
1000 beschreibt frl:6410737
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Thu Jan 30 16:56:39 CET 2020
1000 Objekt bearb. Thu Jan 17 13:30:30 CET 2019
1000 Vgl. frl:6410737
1000 Oai Id
  1. oai:frl.publisso.de:frl:6410737 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
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