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Corrigendum Open Access | 10.1172/JCI185290

LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes

Jingzhong Ding, Anh Tram Nguyen, Kurt Lohman, Michael T. Hensley, Daniel Parker, Li Hou, Jackson Taylor, Deepak Voora, Janet K. Sawyer, Elena Boudyguina, Michael P. Bancks, Alain Bertoni, James S. Pankow, Jerome I. Rotter, Mark O. Goodarzi, Russell P. Tracy, David M. Murdoch, Daniel Duprez, Stephen S. Rich, Bruce M. Psaty, David Siscovick, Christopher B. Newgard, David Herrington, Ina Hoeschele, Steven Shea, James H. Stein, Manesh Patel, Wendy Post, David Jacobs Jr., John S. Parks, and Yongmei Liu

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Published August 15, 2024 - More info

Published in Volume 134, Issue 16 on August 15, 2024
J Clin Invest. 2024;134(16):e185290. https://doi.org/10.1172/JCI185290.
© 2024 Ding et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published August 15, 2024 - Version history
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Related article:

LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes
Jingzhong Ding, … , John S. Parks, Yongmei Liu
Jingzhong Ding, … , John S. Parks, Yongmei Liu
The dysregulated LXRβ/ABCG1-ABCA1-MYLIP signaling pathway, coincident with cellular cholesterol accumulation, is a major risk factor for type 2 diabetes.
Clinical Research and Public Health Metabolism

LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes

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Abstract

BACKGROUND Preclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) — suggestive of cellular cholesterol accumulation — were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought to determine whether the CMTN alterations independently predict incident prediabetes/T2D risk, and correlate with cellular cholesterol accumulation.METHODS Monocyte mRNA expression of 11 CMTN genes was quantified among 934 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of prediabetes/T2D; cellular cholesterol was measured in a subset of 24 monocyte samples.RESULTS During a median 6-year follow-up, lower expression of 3 highly correlated LXR target genes — ABCG1 and ABCA1 (cholesterol efflux) and MYLIP (cholesterol uptake suppression) — and not other CMTN genes, was significantly associated with higher risk of incident prediabetes/T2D. Lower expression of the LXR target genes correlated with higher cellular cholesterol levels (e.g., 47% of variance in cellular total cholesterol explained by ABCG1 expression). Further, adding the LXR target genes to overweight/obesity and other known predictors significantly improved prediction of incident prediabetes/T2D.CONCLUSION These data suggest that the aberrant LXR/ABCG1-ABCA1-MYLIP pathway (LAAMP) is a major T2D risk factor and support a potential role for aberrant LAAMP and cellular cholesterol accumulation in diabetogenesis.FUNDING The MESA Epigenomics and Transcriptomics Studies were funded by NIH grants 1R01HL101250, 1RF1AG054474, R01HL126477, R01DK101921, and R01HL135009. This work was supported by funding from NIDDK R01DK103531 and NHLBI R01HL119962.

Authors

Jingzhong Ding, Anh Tram Nguyen, Kurt Lohman, Michael T. Hensley, Daniel Parker, Li Hou, Jackson Taylor, Deepak Voora, Janet K. Sawyer, Elena Boudyguina, Michael P. Bancks, Alain Bertoni, James S. Pankow, Jerome I. Rotter, Mark O. Goodarzi, Russell P. Tracy, David M. Murdoch, Daniel Duprez, Stephen S. Rich, Bruce M. Psaty, David Siscovick, Christopher B. Newgard, David Herrington, Ina Hoeschele, Steven Shea, James H. Stein, Manesh Patel, Wendy Post, David Jacobs Jr., John S. Parks, Yongmei Liu

×

Original citation: J Clin Invest. 2024;134(10):e173278. https://doi.org/10.1172/JCI173278

Citation for this corrigendum: J Clin Invest. 2024;134(16):e185290. https://doi.org/10.1172/JCI185290

During the preparation of this manuscript, Daniel Duprez’s information was inadvertently omitted from the author list and the Author contributions section of the manuscript. Christopher B. Newgard’s middle initial was also omitted from both. The correct author list, affiliation list, and sentence from the Author contributions section are below. The HTML and PDF versions have been updated.

Jingzhong Ding,1 Anh Tram Nguyen,2 Kurt Lohman,2 Michael T. Hensley,2 Daniel Parker,3 Li Hou,2 Jackson Taylor,4 Deepak Voora,2 Janet K. Sawyer,1 Elena Boudyguina,1 Michael P. Bancks,5 Alain Bertoni,1 James S. Pankow,6 Jerome I. Rotter,7 Mark O. Goodarzi,8 Russell P. Tracy,9 David M. Murdoch,10 Daniel Duprez,11 Stephen S. Rich,12 Bruce M. Psaty,13 David Siscovick,14 Christopher B. Newgard,15 David Herrington,1 Ina Hoeschele,16 Steven Shea,17 James H. Stein,18 Manesh Patel,2 Wendy Post,19 David Jacobs Jr.,6 John S. Parks,1 and Yongmei Liu2

1Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. 2Department of Medicine, Division of Cardiology, and 3Department of Medicine, Division of Geriatrics, Duke University, Durham, North Carolina, USA. 4Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio, USA. 5Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA 6Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA. 7The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA 8Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, USA. 9Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont, USA. 10Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University, Durham, North Carolina, USA. 11Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA. 12Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA. 13Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, Washington, USA. 14New York Academy of Medicine, New York, New York, USA. 15Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA. 16Fralin Life Sciences Institute, Virginia Tech, Blacksburg, Virginia, USA. 17Department of Medicine, Columbia University, New York, New York, USA. 18School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA. 19Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Author contributions

JD, ATN, KL, MTH, DP, LH, JT, DV, JKS, EB, MPB, AB, JSP, HIR, MOG, RPT, DMM, DAD, SSR, BMP, DS, CBN, DH, IH, SSR, JHS, MPB, WP, DJ, JSP, and YL contributed to data curation, formal analysis, and critical revision of the manuscript.

The authors regret the errors.

Footnotes

See the related article at LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes.

Version history
  • Version 1 (August 15, 2024): Electronic publication

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