Abstract
Objective:
The goal of the present study was to identify differences in gene expression between SAT, VAT and EAT depots in Class III severely obese individuals.
Design:
Human subcutaneous (SAT) and visceral (VAT) adipose tissues exhibit differential gene expression profiles. There is little information, however, about the other proximal white adipose tissue, epigastric (EAT), in terms of its function and contribution to metabolism.
Subjects and methods:
Using RNA from adipose biospecimens obtained from Class III severely obese patients undergoing open Roux-en-Y gastric bypass surgery, we compared gene expression profiles between SAT, VAT and EAT, using microarrays validated by real-time quantitative PCR.
Results:
The three depots were found to share 1907 genes. VAT had the greatest number of genes (66) expressed exclusively in this depot, followed by SAT (23), and then EAT (14). Moreover, VAT shared more genes with EAT (65) than with SAT (38). Further analyses using ratios of SAT/EAT, VAT/EAT and SAT/VAT identified specific as well as overlapping networks and pathways of genes representing dermatological diseases, inflammation, cell cycle and growth, cancer and development. Targeted analysis of genes, having a role in adipose tissue development and function, revealed that Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha (PGC1-α) that regulates the precursor of the hormone Irisin (FNCD5) were abundantly expressed in all three fat depots, along with fibroblast growth factors (FGF) FGF1, FGF7 and FGF10, whereas, FGF19 and FGF21 were undetectable.
Conclusions:
These data indicate that EAT has more in common with VAT, suggesting similar metabolic potential. The human epigastric adipose depot could have a significant functional role in metabolic diseases and should be further investigated.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Accession codes
References
Armani A, Mammi C, Marzolla V, Calanchini M, Antelmi A, Rosano GM et al. Cellular models for understanding adipogenesis, adipose dysfunction, and obesity. J Cell Biochem 2010; 110: 564–572.
Haas B, Schlinkert P, Mayer P, Eckstein N . Targeting adipose tissue. Diabetol Metab Syndr 2012; 4: 43.
Urs S, Smith C, Campbell B, Saxton AM, Taylor J, Zhang B et al. Gene expression profiling in human preadipocytes and adipocytes by microarray analysis. J Nutr 2004; 134: 762–770.
Lefebvre AM, Laville M, Vega N, Riou JP, van Gaal L, Auwerx J et al. Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes 1998; 47: 98–103.
Modesitt SC, Hsu JY, Chowbina SR, Lawrence RT, Hoehn KL . Not all fat is equal: differential gene expression and potential therapeutic targets in subcutaneous adipose, visceral adipose, and endometrium of obese women with and without endometrial cancer. Int J Gynecol Cancer 2012; 22: 732–741.
Gil A, Olza J, Gil-Campos M, Gomez-Llorente C, Aguilera CM . Is adipose tissue metabolically different at different sites? Int J Pediatr Obes 2011; 6 (Suppl 1): 13–20.
Billon N, Dani C . Developmental origins of the adipocyte lineage: new insights from genetics and genomics studies. Stem Cell Rev 2012; 8: 55–66.
Fried SK, Kral JG . Sex differences in regional distribution of fat cell size and lipoprotein lipase activity in morbidly obese patients. Int J Obes 1987; 11: 129–140.
Ktotkiewski M, Sjostrom L, Bjorntorp P, Smith U . Regional adipose tissue cellularity in relation to metabolism in young and middle-aged women. Metabolism 1975; 24: 703–710.
Busetto L, Digito M, Dalla Monta P, Carraro R, Enzi G . Omental and epigastric adipose tissue lipolytic activity in human obesity. Effect of abdominal fat distribution and relationship with hyperinsulinemia. Hormone Metabol Res 1993; 25: 365–371.
Paula HA, Ribeiro Rde C, Rosado LE, Abranches MV, Franceschini Sdo C . Classic anthropometric and body composition indicators can predict risk of metabolic syndrome in elderly. Ann Nutr Metab 2012; 60: 264–271.
Poliakova N, Despres JP, Bergeron J, Almeras N, Tremblay A, Poirier P . Influence of obesity indices, metabolic parameters and age on cardiac autonomic function in abdominally obese men. Metabolism 2012; 61: 1270–1279.
Min JL, Nicholson G, Halgrimsdottir I, Almstrup K, Petri A, Barrett A et al. Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes. PLoS Genet 2012; 8: e1002505.
Janiszewski PM, Ross R, Despres JP, Lemieux I, Orlando G, Carli F et al. Hypertriglyceridemia and waist circumference predict cardiovascular risk among HIV patients: a cross-sectional study. PLoS One 2011; 6: e25032.
Mutch DM, Temanni MR, Henegar C, Combes F, Pelloux V, Holst C et al. Adipose gene expression prior to weight loss can differentiate and weakly predict dietary responders. PLoS One 2007; 2: e1344.
Gomez-Ambrosi J, Catalan V, Diez-Caballero A, Martinez-Cruz LA, Gil MJ, Garcia-Foncillas J et al. Gene expression profile of omental adipose tissue in human obesity. FASEB J 2004; 18: 215–227.
Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012; 150: 366–376.
Kelly DP . Medicine. Irisin, light my fire. Science 2012; 336: 42–43.
Matzko ME, Argyropoulos G, Wood GC, Chu X, McCarter RJ, Still CD et al. Association of ghrelin receptor promoter polymorphisms with weight loss following Roux-en-Y gastric bypass surgery. Obes Surg 2012; 22: 783–790.
Still CD, Wood GC, Chu X, Erdman R, Manney CH, Benotti PN et al. High allelic burden of four obesity SNPs is associated with poorer weight loss outcomes following gastric bypass surgery. Obesity 2011; 19: 1676–1683.
Wood GC, Chu X, Manney C, Strodel W, Petrick A, Gabrielsen J et al. An electronic health record-enabled obesity database. BMC Med Inform Decision Making 2012; 12: 45.
Than NG, Romero R, Tarca AL, Draghici S, Erez O, Chaiworapongsa T et al. Mitochondrial manganese superoxide dismutase mRNA expression in human chorioamniotic membranes and its association with labor, inflammation, and infection. J Matern Fetal Neonatal Med 2009; 22: 1000–1013.
Lillvis JH, Erdman R, Schworer CM, Golden A, Derr K, Gatalica Z et al. Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms. BMC Physiol 2011; 11: 9.
Korsic M, Gotovac K, Nikolac M, Dusek T, Skegro M, Muck-Seler D et al. Gene expression in visceral and subcutaneous adipose tissue in overweight women. Front Biosci (Elite Ed) 2012; 4: 2834–2844.
Karastergiou K, Fried SK, Xie H, Lee MJ, Divoux A, Rosencrantz MA et al. Distinct developmental signatures of human abdominal and gluteal subcutaneous adipose tissue depots. J Clin Endocrinol Metabol 2013; 98: 362–371.
Blumberg H, Dinh H, Trueblood ES, Pretorius J, Kugler D, Weng N et al. Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation. J Exp Med 2007; 204: 2603–2614.
Iwasa H, Kurabayashi M, Nagai R, Nakamura Y, Tanaka T . Genetic variations in five genes involved in the excitement of cardiomyocytes. J Hum Genet 2001; 46: 549–552.
Bosanska L, Michalsky D, Lacinova Z, Dostalova I, Bartlova M, Haluzikova D et al. The influence of obesity and different fat depots on adipose tissue gene expression and protein levels of cell adhesion molecules. Physiol Res 2010; 59: 79–88.
Tan BK, Adya R, Randeva HS . Omentin: a novel link between inflammation, diabesity, and cardiovascular disease. Trends Cardiovasc Med 2010; 20: 143–148.
Oberauer R, Rist W, Lenter MC, Hamilton BS, Neubauer H . EGFL6 is increasingly expressed in human obesity and promotes proliferation of adipose tissue-derived stromal vascular cells. Mol Cell Biochem 2010; 343: 257–269.
McLaughlin T, Lamendola C, Liu A, Abbasi F . Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metabol 2011; 96: E1756–E1760.
Jansen BJ, Gilissen C, Roelofs H, Schaap-Oziemlak A, Veltman JA, Raymakers RA et al. Functional differences between mesenchymal stem cell populations are reflected by their transcriptome. Stem Cells Dev 2010; 19: 481–490.
Hart AW, Baeza N, Apelqvist A, Edlund H . Attenuation of FGF signalling in mouse beta-cells leads to diabetes. Nature 2000; 408: 864–868.
Feingold KR, Grunfeld C, Heuer JG, Gupta A, Cramer M, Zhang T et al. FGF21 is increased by inflammatory stimuli and protects leptin-deficient ob/ob mice from the toxicity of sepsis. Endocrinology 2012; 153: 2689–2700.
Flier JS . Hormone resistance in diabetes and obesity: insulin, leptin, and FGF21. Yale J Biol Med 2012; 85: 405–414.
Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481: 463–468.
Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino-Powell K et al. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science 2011; 331: 1621–1624.
Fisher FM, Kleiner S, Douris N, Fox EC, Mepani RJ, Verdeguer F et al. FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev 2012; 26: 271–281.
Acknowledgements
This research was supported by research funds from the Geisinger Clinic and the National Institute of Health grants DK072488 (GSG, CDS, GA) and DK088231 (GSG) and DK091601 (GSG). We would like to thank Dr Charles Schworer and Ms Alicia Golden for help with the microarray experiments and the data analyses.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
Supplementary Information accompanies this paper on International Journal of Obesity website
Supplementary information
Rights and permissions
About this article
Cite this article
Gerhard, G., Styer, A., Strodel, W. et al. Gene expression profiling in subcutaneous, visceral and epigastric adipose tissues of patients with extreme obesity. Int J Obes 38, 371–378 (2014). https://doi.org/10.1038/ijo.2013.152
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijo.2013.152
Keywords
This article is cited by
-
Omics approach to reveal the effects of obesity on the protein profiles of the exosomes derived from different adipose depots
Cellular and Molecular Life Sciences (2022)
-
The impact of obesity on adipocyte-derived extracellular vesicles
Cellular and Molecular Life Sciences (2021)
-
Putative positive role of inflammatory genes in fat deposition supported by altered gene expression in purified human adipocytes and preadipocytes from lean and obese adipose tissues
Journal of Translational Medicine (2020)
-
A retrospective case control study identifies peripheral blood mononuclear cell albumin RNA expression as a biomarker for non-alcoholic fatty liver disease
Langenbeck's Archives of Surgery (2020)
-
Deep transcriptome analysis using RNA-Seq suggests novel insights into molecular aspects of fat-tail metabolism in sheep
Scientific Reports (2019)