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.

IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM
Journal of Obesity Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI:10.1155/2024/4541071
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.

对肥胖女性内脏脂肪组织的芯片分析揭示了炎症、新陈代谢、成瘾行为和癌症之间的共同交叉点:肥胖症中 AKT3 和 MAPK1 的交叉点。
背景:内脏脂肪组织(VAT)异常与肥胖相关疾病直接相关。肥胖症患者内脏脂肪组织病理风险增加的内在机制尚未完全阐明。研究方法进行了一项病例对照研究,其中包括 10 名肥胖女性(36.80 ± 7.39 岁,体重指数≥ 30 kg/m2)和 10 名体重正常女性(32.70 ± 9.45 岁,体重指数< 24.9 kg/m2)。从大网膜活检组织中提取 RNA,并以体重正常的女性为参照,使用 DNA 微阵列评估肥胖女性 VAT 的差异转录组表达。差异表达基因(DEGs)被归类为功能性生物过程和信号通路;此外,还整合了蛋白质相互作用(PPI)网络,以深入分析与肥胖相关的中心性疾病有关的通路和基因。此外,还量化了VAT中TNF-α、MAPK和AKT蛋白的表达。结果显示肥胖症妇女的血管内皮细胞中有 3808 个 DEGs,主要与炎症、碳水化合物和脂质代谢的细胞过程有关。高表达基因与炎症、代谢、激素、神经内分泌、致癌和感染途径有关。与成瘾行为有关的细胞过程值得注意。MAPK和PI3K-AKT通路过度表达,Mapk1和Akt3基因是肥胖相关疾病通路的共同交叉点。肥胖妇女的血管内皮细胞中证实了 MAPK、AKT 和 TNF 蛋白表达的增加。结论肥胖症患者的增值血管具有复杂和混合的致病转录组特征,其异常过程主要受激活的细胞内信号通路控制,这些通路表现出高度的冗余性。确定这些通路之间的共同交叉点可使特定的靶向治疗对多个致病过程产生广泛的影响。
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来源期刊
Journal of Obesity
Journal of Obesity ENDOCRINOLOGY & METABOLISM-
CiteScore
7.50
自引率
3.00%
发文量
19
审稿时长
21 weeks
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.
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