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

Obesity (Silver Spring). 2015 Jun;23(6):1312-9. doi: 10.1002/oby.21079. Epub 2015 May 9.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Cardiac Rehabilitation*
  • Cardiovascular Diseases / genetics*
  • Feeding Behavior
  • Female
  • Gene Expression*
  • Humans
  • Life Style*
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Assessment
  • Risk Reduction Behavior*
  • Weight Loss / genetics*