Laboratorio PABIOM, Facultad de Medicina y Ciencias Biomédicas, Universidad Autónoma de Chihuahua, Chihuahua, Mexico.
Facultad de Medicina y Ciencias Biomédicas, Universidad Autónoma de Chihuahua, Chihuahua, Mexico.
J Obes. 2024 Oct 24;2024:4541071. doi: 10.1155/2024/4541071. eCollection 2024.
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. A case-control study was conducted that included 10 women with obesity (36.80 ± 7.39 years, BMI ≥ 30 kg/m) and 10 women of normal weight (32.70 ± 9.45 years, BMI < 24.9 kg/m). 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-, MAPK, and AKT proteins was also quantified in VAT. 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. 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.
内脏脂肪组织 (VAT) 异常与肥胖相关疾病直接相关。肥胖中 VAT 增加病理风险的潜在机制尚未完全描述。进行了一项病例对照研究，纳入了 10 名肥胖女性（36.80±7.39 岁，BMI≥30kg/m）和 10 名正常体重女性（32.70±9.45 岁，BMI<24.9kg/m）。从大网膜活检组织中提取 RNA，使用 DNA 微阵列评估肥胖女性 VAT 的差异转录组表达，并以正常体重女性的表达为参考。将差异表达基因 (DEG) 分类为功能生物过程和信号通路；此外，整合蛋白质-蛋白质相互作用 (PPI) 网络，以更深入地分析与中心性肥胖相关疾病相关的途径和基因。还定量测定了 VAT 中 TNF-、MAPK 和 AKT 蛋白的表达。肥胖女性的 VAT 有 3808 个 DEG，主要与炎症和碳水化合物及脂质代谢的细胞过程有关。过表达的基因与炎症、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 途径过表达，Mapk1 和 Akt3 基因是肥胖相关疾病途径的共同交叉点。在肥胖女性的 VAT 中，MAPK、AKT 和 TNF 蛋白的表达增加得到了证实。肥胖患者的 VAT 赋予了复杂的、混合的致病转录组谱，其中异常过程主要通过激活表现出高度冗余的细胞内信号通路来控制。确定这些途径之间的共享交叉点可以允许针对特定靶点的治疗对多种致病过程产生广泛影响。
