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Journal of Obesity
Volume 2011, Article ID 265417, 13 pages
Research Article

Differential Effects of Calorie Restriction and Exercise on the Adipose Transcriptome in Diet-Induced Obese Mice

1Department of Nutritional Sciences, University of Texas, Austin, TX 78712, USA
2Department of Molecular Carcinogenesis, UT-MD Anderson Cancer Center, Smithville, TX 78957, USA
3Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712, USA
4Cancer Prevention Fellowship Program, National Cancer Institute, Bethesda, MD 20852, USA

Received 9 December 2010; Accepted 1 March 2011

Academic Editor: P. Trayhurn

Copyright © 2011 Karrie E. Wheatley et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We tested the hypothesis that obesity reversal by calorie restriction (CR) versus treadmill exercise (EX) differentially modulates adipose gene expression using 48 female C57BL/6 mice administered a diet-induced obesity (DIO) regimen for 8 weeks, then randomized to receive for 8 weeks either: (1) a control (AIN-76A) diet, fed ad libitum (DIO control); (2) a 30% CR regimen; (3) a treadmill EX regimen (with AIN-76A diet fed ad libitum); or (4) continuation of the DIO diet. Relative to the DIO controls, both CR and EX reduced adiposity by 35–40% and serum leptin levels by 80%, but only CR increased adiponectin and insulin sensitivity. Gene expression microarray analysis of visceral white adipose tissue revealed 209 genes responsive to both CR and EX, relative to the DIO group. However, CR uniquely altered expression of an additional 496 genes, whereas only 20 were uniquely affected by EX. Of the genes distinctly responsive to CR, 17 related to carbohydrate metabolism and glucose transport, including glucose transporter (GLUT) 4. Chromatin immunoprecipitation assays of the Glut4 promoter revealed that, relative to the DIO controls, CR significantly increased histone 4 acetylation, suggesting epigenetic regulation may underlie some of the differential effects of CR versus EX on the adipose transcriptome.