TY - JOUR
T1 - Importance of substantial weight loss for altering gene expression during cardiovascular lifestyle modification
AU - Ellsworth, Darrell L.
AU - Mamula, Kimberly A.
AU - Blackburn, Heather L.
AU - McDyer, Fionnuala A.
AU - Jellema, Gera L.
AU - Van Laar, Ryan
AU - Costantino, Nicholas S.
AU - Engler, Renata J.M.
AU - Vernalis, Marina N.
N1 - Publisher Copyright:
© 2015 The Obesity Society.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84929943713&partnerID=8YFLogxK
U2 - 10.1002/oby.21079
DO - 10.1002/oby.21079
M3 - Article
C2 - 25960328
AN - SCOPUS:84929943713
SN - 1930-7381
VL - 23
SP - 1312
EP - 1319
JO - Obesity
JF - Obesity
IS - 6
ER -