Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access
Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc
Journal website http://www.jofem.org

Original Article

Volume 5, Number 3, June 2015, pages 199-210

Global Gene Expression Profiling in Omental Adipose Tissue of Morbidly Obese Diabetic African Americans

Figures

Figure 1.
Figure 1. Classification of DEGs among morbidly obese diabetes into biological functions. (A) Pie chart represents all biological functions represented by the 68 DEGs; metabolic and cellular processes denote the two biological classes the most represented. (B) Pie chart represents a breakdown of the metabolic processes shown on A. (C) Pie chart represents a breakdown of the cellular processes shown on A.
Figure 2.
Figure 2. Top canonical pathways enriched among DEGs of morbidly obese diabetics. (A) Telomere extension by telomerase with overlay of glucose uptake function through TNSK2. (B) Regulation of actin-based motility by rho with intersection of D-myo-inositol (1,4,5)-triphosphate biosynthesis through PIP5K and interaction with type 2 diabetes signaling pathway.
Figure 3.
Figure 3. Top three networks showing interactions between selected differentially expressed genes in morbidly obese diabetics. Red: transcripts up-regulated in morbidly obese/diabetic AA; green: transcripts down-regulated in morbidly obese/diabetic AA; white: transcripts not differentially expressed in our study but important in the network. The color gradient in the network indicates the strength of expression denoted by FC. → indicates direct interaction between transcript products; ---> indicates indirect interaction between transcript products; (○) indicates autoregulation. (A) Network 1 with overlay of type 2 diabetic signaling and two of the most significant canonical pathways observed among a number of DEGs. (B) Network 2 representing 16 of the DEGs associated with dermatological diseases and conditions as well as developmental and hereditary diseases. (C) Network 3 representing 14 of the DEGs associated with RNA post-transcriptional modifications, metabolic disease, and cellular development.
Figure 4.
Figure 4. Upstream analysis: network interactions between the five top transcriptional regulators and their target DEGs in morbidly obese diabetics. Orange identifies activated upstream regulators. Green identifies down-regulated target DEGs whereas red identifies up-regulated DEGs. Blunt arrowhead indicates inhibition of the target DEG. Purple indicates genes or regulator that overlay with T2D (4 DEGs + 3 upstream regulators).
Figure 5.
Figure 5. Scatter plot showing relationship between microarray and RT-PCR data for selected transcripts. Diagonal line represents the regression line.

Tables

Table 1. Characteristics of the Study Participants
 
ParametersObese non diabetic (control: n = 6)Obese diabetic (cases: n = 14)P-value
Values presented are mean ± standard deviation; values in parenthesis are ranges. Mean between groups were compared by Student’s t-test. FBG: fasting blood glucose.
Age (years)41.0 ± 4.6 (36 - 47)41.5 ± 9.1 (27 - 61)0.87
BMI (kg/m2)53.9 ± 7.1 (45.6 - 65)54.9 ± 7.8 (44.1 - 73.5)0.79
Waist (inches)N/A55.8 ± 3.3 (51 - 60)-
FBG (mg/dL)N/A128.1 ± 25.5 (81 - 172)-

 

Table 2. List of the most highly differentiated genes in omental adipose tissue of morbidly obese and diabetic African Americans
 
Gene symbolGene nameFCP-valueFDR
FC: fold change; FDR: false discovery rate.
Upregulated transcripts
  MYO10Myosin X2.31.1 × 10-43.8 × 10-2
  TBRG1Transforming growth factor beta regulator 12.01.8 × 10-44.9 × 10-2
Downregulated transcripts
  MALAT1Metastasis associated lung adenocarcinoma transcript 1 (non-protein coding)-9.81.4 × 10-74.9 × 10-4
  MAGOHProliferation-associated (Drosophila)-6.83.6 × 10-51.9 × 10-2
  NR1D2Nuclear receptor subfamily 1, group D, member 2-6.51.1 × 10-59.3 × 10-3
  HIRAHistone cell cycle regulator-6.53.0 × 10-81.8 × 10-4
  PDIA3Protein disulfide isomerase family A, member 3-5.81.5 × 10-74.9 × 10-4
  ARPC3Actin related protein 2/3 complex, subunit 3, 21 kDa-5.01.0 × 10-81.6 × 10-4
  HNRNPA1Heterogeneous nuclear ribonucleoprotein A1-4.51.1 × 10-43.8 × 10-2
  HIVEP2Human immunodeficiency virus type I enhancer binding protein 2-4.43.7 × 10-51.9 × 10-2
  NBPF10Neuroblastoma breakpoint family member 21-like-4.42.4 × 10-63.4 × 10-3
  NUCKS1Nuclear casein kinase and cyclin-dependent kinase substrate 1-4.15.7 × 10-52.6 × 10-2

 

Table 3. List of the Most Significant Canonical Pathways Among the 68 DEGs (Based on Core Analysis in Ingenuity Pathway Analysis (IPA)
 
DescriptionP-valueMolecules
Telomere extension by telomerase1.35 × 10-3HNRNPA1, TNKS2
D-myo-inositol (1,4,5)-trisphosphate biosynthesis3.36 × 10-3PIP5K1A, PIP4K2A
Regulation of actin-based motility by rho3.59 × 10-3PIP5K1A, ARPC3, PIP4K2A
Rac signaling6.79 × 10-3PIP5K1A, ARPC3, PIP4K2A
RhoA signaling7.38 × 10-3PIP5K1A, ARPC3, PIP4K2A

 

Table 4. Biological Functions and Diseases Associated With the Top Ranked Networks
 
Top functionsScoreFocus moleculesNetwork scheme
Infectious disease, neurological disease, cancer4922Figure 3A
Dermatological diseases and conditions, developmental disorder, hereditary disorder3216Figure 3B
RNA post-transcriptional modification, metabolic disease, cellular development2714Figure 3C
Cell-to-cell signaling and interaction, cellular assembly and organization, tissue development2011-