Alotaiq Nasser, Khalifa Ahmed S, Youssef Amr, El-Nagar Esraa G, Elwali Nasr Eldin, Habib Hosam M, AlZaim Ibrahim, Eid Ali H, Bakkar Nour-Mounira Z, El-Yazbi Ahmed F
Health Sciences Research Center, Imam Muhammad Ibn Saud Islamic University (IMISIU), Riyadh, Kingdom of Saudi Arabia.
Faculty of Pharmacy, Alamein International University, Alamein, Egypt.
FASEB J. 2024 Dec 13;38(24):e70273. doi: 10.1096/fj.202402470R.
Individuals with metabolic syndrome have a high risk of developing cardiovascular disorders that is closely tied to visceral adipose tissue dysfunction, as well as an altered interaction between adipose tissue and the cardiovascular system. In metabolic syndrome, adipose tissue dysfunction is associated with increased hypertrophy, reduced vascularization, and hypoxia of adipocytes, leading to a pro-oxidative and pro-inflammatory environment. Among the pathways regulating adipose tissue homeostasis is the wingless-type mammary tumor virus integration site family (Wnt) signaling pathway, with both its canonical and non-canonical arms. Various modulators of the Wnt signaling have been identified to contribute to the development of metabolic diseases and their cardiovascular complications, with a particularly significant role played by Glycogen Synthase Kinase-3β (GSK-3β). GSK-3β levels and activities have various and often contrasting roles in obesity and related metabolic disorders, as well as their cardiovascular sequelae. Here, we explore the possibility that altered Wnt signaling and GSK-3β activities could serve as a connection between adipose tissue dysfunction and the development of cardiovascular disease in individuals with metabolic syndrome. We attempt to define a context-specific approach for intervention, which could possibly serve as a novel disease modifying therapy for the mitigation of such complications.
患有代谢综合征的个体发生心血管疾病的风险很高，这与内脏脂肪组织功能障碍以及脂肪组织与心血管系统之间相互作用的改变密切相关。在代谢综合征中，脂肪组织功能障碍与脂肪细胞肥大增加、血管生成减少和缺氧有关，导致促氧化和促炎环境。调节脂肪组织稳态的途径之一是无翅型乳腺肿瘤病毒整合位点家族（Wnt）信号通路，包括其经典和非经典分支。已确定Wnt信号的各种调节因子会导致代谢疾病及其心血管并发症的发生，糖原合酶激酶-3β（GSK-3β）发挥了特别重要的作用。GSK-3β的水平和活性在肥胖及相关代谢紊乱及其心血管后遗症中具有多种且往往相互矛盾的作用。在此，我们探讨了Wnt信号改变和GSK-3β活性可能是代谢综合征患者脂肪组织功能障碍与心血管疾病发生之间联系的可能性。我们试图确定一种针对具体情况的干预方法，这可能成为减轻此类并发症的新型疾病改良疗法。
