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Clinical Trial
. 2015 Jun;23(6):1312-9.
doi: 10.1002/oby.21079. Epub 2015 May 9.

Importance of Substantial Weight Loss for Altering Gene Expression During Cardiovascular Lifestyle Modification

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Clinical Trial

Importance of Substantial Weight Loss for Altering Gene Expression During Cardiovascular Lifestyle Modification

Darrell L Ellsworth et al. Obesity (Silver Spring). .
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Abstract

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.

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