Karastergiou, Kalypso, Fried, Susan K., Xie, Hui, Lee, Mi-Jeong, Divoux, Adeline, Rosencrantz, Marcus A., Chang, R. Jeffrey, Smith, Steven R.
funding text
This work was supported by National Institutes of Health Grants DK072476, R24DK087669, and P30DK46200; the Society for Women's Health Research Interdisciplinary Studies on Sex Differences (ISIS) Network on Metabolism; the Evans Center for Interdisciplinary Biomedical Research Affinity Research Collaborative on Sex Differences in Adipose Tissue at Boston University School of Medicine; the Genomics Core Facility at the Pennington Biomedical Research Center; and the Geriatric Research Education Clinical Center, Baltimore Veterans Affairs Medical Center. The authors would like to thank the ISIS network and the members of the ISIS group, Jennifer Lovejoy, Nori Geary, Joel Elmquist, Philipp Scherer, Randy Seeley, and Richard Simerly, for their support of this research.
abstract
Context: Fat distribution differs in men and women, but in both sexes, a predominantly gluteal-femoral compared with abdominal (central) fat distribution is associated with lower metabolic risk. Differences in cellular characteristics and metabolic functions of these depots have been described, but the molecular mechanisms involved are not understood. Objective: Our objective was to identify depot-and sex-dependent differences in gene expression in human abdominal and gluteal sc adipose tissues. Design and Methods: Abdominal and gluteal adipose tissue aspirates were obtained from 14 premenopausalwomen [age 27.5 +/- 7.0 yr, bodymass index (BMI) 27.3 +/- 6.2 kg/m(2), andwaist-to-hip ratio 0.82 +/- 0.04] and 21 men (age 29.7 +/- 7.4 yr, BMI 27.2 +/- 4.5 kg/m(2), and waist-to-hip ratio 0.91 +/- 0.07) and transcriptomes were analyzed using Illumina microarrays. Expression of selected genes was determined in isolated adipocytes and stromal vascular fractions from each depot, and in in vitro cultures before and after adipogenic differentiation. Results: A total of 284 genes were differentially expressed between the abdominal and gluteal depot, either specifically in males (n = 66) or females (n = 159) or in both sexes (n = 59). Most notably, gene ontology and pathway analysis identified homeobox genes (HOXA2, HOXA3, HOXA4, HOXA5, HOXA9, HOXB7, HOXB8, HOXC8, and IRX2) that were down-regulated in the gluteal depot in both sexes (P = 2 x 10(-10)). Conversely, HOXA10 was up-regulated in gluteal tissue and HOXC13 was detected exclusively in this depot. These differences were independent of BMI, were present in both adipocytes and stromal vascular fractions of adipose tissue, and were retained throughout in vitro differentiation. Conclusions: We conclude that developmentally programmed differences may contribute to the distinct phenotypic characteristics of peripheral fat. (J Clin Endocrinol Metab 98: 362-371, 2013)