Department of Pharmacology and Toxicology, Al-Azhar University, Faculty of Pharmacy, Cairo, Egypt.
Research Institute of Pediatrics, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China.
Chem Biol Interact. 2022 Oct 1;366:110141. doi: 10.1016/j.cbi.2022.110141. Epub 2022 Sep 2.
Obesity is the leading risk factor associated with Metabolic dysfunction Associated with Fatty Liver Disease (MAFLD), Insulin Resistance (IR), and type 2 diabetes (T2DM). Notably, MAFLD affects 25% of the world's adult population, ranging from 13.5% in Africa to 31.8% in the Middle East. The prevalence of MAFLD is 80-90% in obese adults and 30-50% in patients with diabetes. According to the recent WHO update, more than 400 million people will experience T2DM by 2025. Furthermore, the worldwide obesity incidence rate has risen in the preceding years. Adipogenesis deterioration is a critical step in the induction of obesity correlated with MAFLD, IR and T2DM. The well-known transcription factor GATA3 is highly expressed in the preadipocytes-adipocytes transition of embryonic stem cells and obese people with IR. In this regard, the reduction of GATA3 improves the differentiation of adipocytes. Omental adipose tissue inflammation by upregulation of macrophages infiltration is strongly linked with body mass index in insulin tolerance of obese people. In particular, the dynamic interaction between macrophages and adipocytes significantly regulates obese adipose tissue's inflammatory status and influences IR by reducing the differentiation of adipocytes, macrophage function, and glucose transport. Emerging evidence demonstrated that GATA3 is a master regulator for macrophage polarization and infiltration. Hence, we will shed light on GATA3 as an emerging target for immunomodulation in human obesity associated with MAFLD, IR, and T2DM by reducing macrophages' recruitment and inflammation of muscles and liver.
肥胖是与代谢功能障碍相关的非酒精性脂肪性肝病 (MAFLD)、胰岛素抵抗 (IR) 和 2 型糖尿病 (T2DM) 相关的主要风险因素。值得注意的是，MAFLD 影响全球成年人口的 25%，范围从非洲的 13.5%到中东的 31.8%。肥胖成年人中 MAFLD 的患病率为 80-90%，糖尿病患者中为 30-50%。根据世界卫生组织最近的更新，到 2025 年，将有超过 4 亿人患有 T2DM。此外，全球肥胖发病率在过去几年中有所上升。脂肪生成恶化是诱导与 MAFLD、IR 和 T2DM 相关的肥胖的关键步骤。众所周知的转录因子 GATA3 在胚胎干细胞和肥胖伴 IR 个体的前脂肪细胞-脂肪细胞转化中高度表达。在这方面，GATA3 的减少可改善脂肪细胞的分化。巨噬细胞浸润引起的网膜脂肪组织炎症与肥胖人群胰岛素耐量的体重指数密切相关。特别是，巨噬细胞和脂肪细胞之间的动态相互作用可通过减少脂肪细胞分化、巨噬细胞功能和葡萄糖转运来显著调节肥胖脂肪组织的炎症状态并影响 IR。新出现的证据表明，GATA3 是巨噬细胞极化和浸润的主要调节因子。因此，我们将重点介绍 GATA3 作为减少肌肉和肝脏中巨噬细胞募集和炎症的人类肥胖相关 MAFLD、IR 和 T2DM 免疫调节的新兴靶点。
