Microarray Analysis of Visceral Adipose Tissue in Obese Women Reveals Common Crossroads Among Inflammation, Metabolism, Addictive Behaviors, and Cancer: AKT3 and MAPK1 Cross Point in Obesity.
Rolando Martínez-Romero, Susana Aideé González-Chávez, Victor Roberto Urías-Rubí, Víctor Manuel Gómez-Moreno, Manlio Favio Blanco-Cantero, Héctor Mario Bernal-Velázquez, Arturo Luévano-González, César Pacheco-Tena
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引用次数: 0
Abstract
Background: Visceral adipose tissue (VAT) abnormalities are directly associated with obesity-associated disorders. The underlying mechanisms that confer increased pathological risk to VAT in obesity have not been fully described. Methods: A case-control study was conducted that included 10 women with obesity (36.80 ± 7.39 years, BMI ≥ 30 kg/m2) and 10 women of normal weight (32.70 ± 9.45 years, BMI < 24.9 kg/m2). RNA was extracted from greater omentum biopsies, and, using a DNA microarray, differential transcriptomic expression of VAT in women with obesity was evaluated taking as a reference that of women with normal weight. The differentially expressed genes (DEGs) were classified into functional biological processes and signaling pathways; moreover, the protein-protein interaction (PPI) networks were integrated for a deeper analysis of the pathways and genes involved in the central obesity-associated disorders. The expression of TNF-α, MAPK, and AKT proteins was also quantified in VAT. Results: The VAT of women with obesity had 3808 DEGs, mainly associated with the cellular process of inflammation and carbohydrates and lipid metabolism. Overexpressed genes were associated with inflammatory, metabolic, hormonal, neuroendocrine, carcinogenic, and infectious pathways. Cellular processes related to addictive behaviors were notable. MAPK and PI3K-AKT pathways were overexpressed, and Mapk1 and Akt3 genes were common crossing points among obesity-associated disorders' pathways. The increased expression of MAPK, AKT, and TNF proteins was confirmed in the VAT of women with obesity. Conclusion: VAT confers a complex and blended pathogenic transcriptomic profile in obese patients, where abnormal processes are mainly controlled by activating intracellular signaling pathways that exhibit a high degree of redundancy. Identifying shared cross points between those pathways could allow specific targeting treatments to exert a widespread effect over multiple pathogenic processes.
期刊介绍:
Journal of Obesity is a peer-reviewed, Open Access journal that provides a multidisciplinary forum for basic and clinical research as well as applied studies in the areas of adipocyte biology & physiology, lipid metabolism, metabolic syndrome, diabetes, paediatric obesity, genetics, behavioural epidemiology, nutrition & eating disorders, exercise & human physiology, weight control and health risks associated with obesity.