Importance of substantial weight loss for altering gene expression during cardiovascular lifestyle modification

Darrell L. Ellsworth*, Kimberly A. Mamula, Heather L. Blackburn, Fionnuala A. McDyer, Gera L. Jellema, Ryan Van Laar, Nicholas S. Costantino, Renata J.M. Engler, Marina N. Vernalis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Objective To examine relationships between weight loss through changes in lifestyle and peripheral blood gene expression profiles. Methods A prospective nonrandomized trial was conducted over 1 year in participants undergoing intensive lifestyle modification to reverse or stabilize progression of coronary artery disease. Cardiovascular risk factors, inflammatory biomarkers, and gene expression as a function of weight loss were assessed in 89 lifestyle participants and 71 retrospectively matched controls undergoing usual care. Results Substantial weight loss (-15.2±3.8%) in lifestyle participants (n=33) was associated with improvement in selected cardiovascular risk factors and significant changes in peripheral blood gene expression from pre- to post-intervention: 132 unique genes showed significant expression changes (false discovery rate corrected P-value <0.05 and fold-change ≥1.4). Altered molecular pathways were related to immune function and inflammatory responses involving endothelial activation. In contrast, participants losing minimal weight (-3.1±2.5%, n=32) showed only minor changes in cardiovascular risk factors and markers of inflammation and no changes in gene expression compared to non intervention controls after 1 year. Conclusions Weight loss (≥10%) during lifestyle modification is associated with down-regulation of genetic pathways governing interactions between circulating immune cells and the vascular endothelium and may be required to successfully reduce CVD risk.

Original languageEnglish
Pages (from-to)1312-1319
Number of pages8
Issue number6
StatePublished - 1 Jun 2015
Externally publishedYes


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