Global Gene Expression Profiling in Omental Adipose Tissue of Morbidly Obese Diabetic African Americans.
BACKGROUND
Adipose tissues play important role in the pathophysiology of obesity-related diseases including type 2 diabetes (T2D). To describe gene expression patterns and functional pathways in obesity-related T2D, we performed global transcript profiling of omental adipose tissue (OAT) in morbidly obese individuals with or without T2D.


METHODS
Twenty morbidly obese (mean BMI: about 54 kg/m2) subjects were studied, including 14 morbidly obese individuals with T2D (cases) and 6 morbidly obese individuals without T2D (reference group). Gene expression profiling was performed using the Affymetrix U133 Plus 2.0 human genome expression array. Analysis of covariance was performed to identify differentially expressed genes (DEGs). Bioinformatics tools including PANTHER and Ingenuity Pathway Analysis (IPA) were applied to the DEGs to determine biological functions, networks and canonical pathways that were overrepresented in these individuals.


RESULTS
At an absolute fold-change threshold of 2 and false discovery rate (FDR) < 0.05, 68 DEGs were identified in cases compared to the reference group. Myosin X (MYO10) and transforming growth factor beta regulator 1 (TBRG1) were upregulated.MYO10encodes for an actin-based motor protein that has been associated with T2D. Telomere extension by telomerase (HNRNPA1, TNKS2), D-myo-inositol (1, 4, 5)-trisphosphate biosynthesis (PIP5K1A, PIP4K2A), and regulation of actin-based motility by Rho (ARPC3) were the most significant canonical pathways and overlay with T2D signaling pathway. Upstream regulator analysis predicted 5 miRNAs (miR-320b, miR-381-3p, miR-3679-3p, miR-494-3p, and miR-141-3p,) as regulators of the expression changes identified.


CONCLUSIONS
This study identified a number of transcripts and miRNAs in OAT as candidate novel players in the pathophysiology of T2D in African Americans.
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
Ayo P
AP
Doumatey
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD ; University of Maryland, School of Medicine, Baltimore, MD.
Huichun
H
Xu
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
Hanxia
H
Huang
Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
Niraj S
NS
Trivedi
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
Lin
L
Lei
Core laboratory-Cancer Genetics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
Abdel
A
Elkahloun
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
Adebowale
A
Adeyemo
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
Charles N
CN
Rotimi
African Americans; Global gene expression; Obesity; Type 2 diabetes