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Obesity (Silver Spring). 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.

Author information

1
Integrative Cardiac Health Program, Windber Research Institute, Windber, Pennsylvania, USA.
2
Almac Diagnostics, Almac Group Limited, Craigavon, UK.
3
Bioinformatics Department, ChipDX LLC, New York, New York, USA.
4
Integrative Cardiac Health Program, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.

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.

PMID:
25960328
DOI:
10.1002/oby.21079
[Indexed for MEDLINE]
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