title: Gene expression regional differences in human subcutaneous adipose tissue.
abstract: Accumulation of visceral adipose tissue (VAT) is clearly associated with an increased risk of obesity-related diseases and all-cause mortality, whereas gluteal subcutaneous fat accumulation (g-SAT) is associated with a lower risk. The relative contribution, in term of cardiovascular risk, of abdominal subcutaneous adipose tissue (a-SAT) is still controversial with studies showing both a detrimental effect and a protective role. Animal and in vitro studies demonstrated that adipocytes from visceral and subcutaneous depots have distinct morphological, metabolic and functional characteristics. These regional differences have a key role in the pathogenesis of obesity-related diseases. There is recent evidence that differentiation between upper-body and lower-body adipose tissues might be under control of site-specific sets of developmental genes, such as Homebox (HOX) genes, a group of related genes that control the body plan of an embryo along the anterior-posterior axis. However, the possible heterogeneity between different subcutaneous regions has not been extensively investigated. Here we studied global mRNA expression in g-SAT and a-SAT with a microarray approach. RNA was isolated from g-SAT and a-SAT biopsy, from eight healthy subjects, and hybridized on RNA microarray chips in order to detect regional differences in gene expression.
  
  
  
  A total of 131 genes are significantly and differently (>1.5 fold change, p < 0.05) expressed in a-SAT and g-SAT. Expression profiling reveals significant differences in expression of several HOX genes. Interestingly, two molecular signature of visceral adipocyte lineage, homebox genes HOXA5 and NR2F1, are up-regulated in a-SAT versus g-SAT by a 2.5 fold change.
  
  
  
  Our study shows that g-SAT and a-SAT have distinct expression profiles. The finding of a different expression of HOX genes, fundamental during the embryo development, suggests an early regional differentiation of subcutaneous adipose depots. Moreover, the higher expression of HOXA5 and NR2F1, two molecular signatures of visceral adipocytes, in a-SAT suggests that this subcutaneous adipose depot could be more similar to VAT than g-SAT. Our data suggest that we should look at SAT as composed of distinct depots with possibly different impact in obesity associated metabolic complications.
authors.affiliation: Azienda Ospedaliero Universitaria di Ferrara, Ferrara, Italy. psn@unife.it.|Department of Medical Sciences, Section of Internal Medicine and CardioRespiratory, University of Ferrara, Ferrara, Italy. psn@unife.it.
authors.forename: Angelina
authors.identifier: 0000-0001-8462-7000
authors.initials: A
authors.lastname: Passaro
authors.affiliation: Azienda Ospedaliero Universitaria di Ferrara, Ferrara, Italy.|Department of Medical Sciences, Section of Internal Medicine and CardioRespiratory, University of Ferrara, Ferrara, Italy.
authors.forename: Maria Agata
authors.initials: MA
authors.lastname: Miselli
authors.affiliation: Department of Medical Sciences, Section of Internal Medicine and CardioRespiratory, University of Ferrara, Ferrara, Italy.
authors.forename: Juana Maria
authors.initials: JM
authors.lastname: Sanz
authors.affiliation: Azienda Ospedaliero Universitaria di Ferrara, Ferrara, Italy.|Department of Medical Sciences, Section of Internal Medicine and CardioRespiratory, University of Ferrara, Ferrara, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Dalla Nora
authors.affiliation: Azienda Ospedaliero Universitaria di Ferrara, Ferrara, Italy.|Department of Medical Sciences, Section of Internal Medicine and CardioRespiratory, University of Ferrara, Ferrara, Italy.
authors.forename: Mario Luca
authors.initials: ML
authors.lastname: Morieri
authors.affiliation: Azienda Ospedaliero Universitaria di Ferrara, Ferrara, Italy.|Department of Medical Sciences, Section of Internal Medicine and CardioRespiratory, University of Ferrara, Ferrara, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Colonna
authors.affiliation: Science and Research Centre, University of Primorska, Koper, 6000, Slovenia.
authors.forename: Rado
authors.initials: R
authors.lastname: Pišot
authors.affiliation: Azienda Ospedaliero Universitaria di Ferrara, Ferrara, Italy.|Department of Medical Sciences, Section of Internal Medicine and CardioRespiratory, University of Ferrara, Ferrara, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zuliani
mesh_terms: D000368:Aged; D015415:Biomarkers; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity / Q000235:genetics; D050151:Subcutaneous Fat / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D015415:Biomarkers
keywords: Adipose tissue; Homeobox genes; Microarray; Obesity; SAT; VAT