Abstract 3559: Gene-expression changes in adipose tissue with diet- and/or exercise-induced weight loss: a randomized controlled trial
Authors: Foster-Schubert Karen , Campbell Kristin , Kratz Mario , Makar Karen W. , Hagman Derek , Schur Ellen A. , Horton Marc , Habermann Nina , Abbenhardt Clare S. , Xiao Liren , Wang Ching-Yun , Duggan Catherine R. , Tiernan Anne Mc , Ulrich Cornelia M. 
Published: August 2012

Background: Adipose tissue (AT) plays a role in obesity-related disease pathogenesis via increased production of inflammatory factors, steroid hormones, and altered lipid metabolism. The impact of diet and/or exercise induced weight loss on AT gene expression will provide key insights into the pathways linking obesity with metabolic disease. Methods: We conducted an ancillary study within a randomized trial of calorie-reduced diet (D), exercise (E), or combined diet and exercise (D+E) vs control among overweight/obese postmenopausal women (Nutrition and Exercise for Women Study). Subcutaneous AT was biopsied at baseline and 6 months from 47 women. Gene expression was measured by the Illumina BeadChip WG-6 and interrogated for changes in candidate genes, and all array-based genes. Analyses were conducted by intervention group and by weight-loss group. Results: Participants were aged 58.3±4.7 years; with a mean BMI of 31.1±4.3 kg/m2. At 6 month, controls were weight-stable while D, E, and D+E participants lost on average 8.8 kg, 2.5 kg, and 7.9 kg (all P&lt;0.05 vs control). There were no significant changes in candidate gene expression by intervention group. When all participants were analyzed by weight loss, in the group with &gt;10% weight loss there was a progressive decrease in 17α hydroxysteroid dehydrogenase-1 (-35% p-trend=0.0002), steroid sulfatase (-26%, p-trend=0.02), 17α hydroxysteroid dehydrogenase-10 (-5%, p-trend=0.045), intercellular adhesion molecule 4 (-9%, p-trend=0.01), serum amyloid A (-38%, p-trend=0.01), and leptin (-44%, p-trend=0.00003) expression, with trends towards increased expression of estrogen receptor-1 (24% p-trend=0.004), C-reactive protein (23%, p-trend 0.008), vascular cell adhesion molecule 1 (34%, p-trend=0.04) and insulin-like growth factor (IGF) binding protein-3 (37%; p-trend=0.003). The unsupervised clustering of &gt;37.000 transcripts by weight loss revealed 78 transcripts with statistically significant adjusted p-values. Leptin, the strongest signal in our candidate-gene analysis, was the 33rd strongest hit in this clustering. Conclusions: A 6-month lifestyle intervention caused weight loss with corresponding changes in AT gene expression, particularly steroid-hormone metabolism and IGF signaling, both pathways postulated to link obesity and cancer. Leptin is a primary signaling target of weight loss in adipose tissue, but weight change altered also a number of other biologic pathways in adipose tissue which requires further investigation.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3559. doi:1538-7445.AM2012-3559