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

Ayo P. Doumatey, Huichun Xu, Hanxia Huang, Niraj S. Trivedi, Lin Lei, Abdel Elkahloun, Adebowale Adeyemo, Charles N. Rotimi

Abstract


Background: Adipose tissues play an 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 six 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) of < 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. MYO10 encodes 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 five miRNAs (miR-320b, miR-381-3p, miR-3679-3p, miR-494-3p, and miR-141-3p), as regulators of the expression changes identified.

Conclusion: This study identified a number of transcripts and miRNAs in OAT as candidate novel players in the pathophysiology of T2D in African Americans.




J Endocrinol Metab. 2015;5(3):199-210
doi: http://dx.doi.org/10.14740/jem286w


Keywords


Obesity; Global gene expression; Type 2 diabetes; African Americans

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