Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Ir. Soekarno Km 21, Jatinangor 45363, Indonesia.
Prodia Clinical Laboratory, Jl. Kramat Raya 150, Jakarta 10430, Indonesia.
J Obes. 2024 Mar 20;2024:1424404. doi: 10.1155/2024/1424404. eCollection 2024.
Obesity is expected to hinder efferocytosis due to ADAM17-mediated cleavage of the MER tyrosine kinase receptor, producing soluble MER (sMER) that disrupts MERTK binding to cell death markers. However, the intracellular efferocytosis pathway in central obesity remains elusive, particularly the role of low-grade chronic inflammation in its initiation and identification of binding signals that disrupt efferocytosis.
We investigate the efferocytosis signaling pathway in men with central obesity and its relationship with inflammation, cell death, and related processes.
A cross-sectional study was conducted, and clinical data and blood samples were collected from 56 men with central obesity (obese group) and 29 nonobese individuals (control group). Clinical evaluations and predefined biochemical screening tests were performed. The efferocytosis signaling pathway was investigated by measuring phosphatidylserine (PS), ADAM17, TNF-alpha (TNF-), and sMER.
Metabolic syndrome was detected in more than half of the participants in the obese group according to the predefined tests. Mean levels of PS, TNF-, and sMER were higher in the obese group but not significantly different from those of the control group. Further analysis based on waist circumference (WC) ranges in the obese group revealed a significant increase in PS and sMER levels between the control group and the obese group with WC greater than 120 cm. ADAM17 levels were significantly higher in the obese group than in the control group. PS was positively correlated with WC and ADAM17. ADAM17 was positively correlated with TNF- and sMER, indicating impaired efferocytosis.
Central obesity appeared to cause a disturbance in efferocytosis that began with cell damage and death, along with an enlargement of the WC and an ongoing inflammatory response. Efferocytosis was disrupted by proinflammatory cytokine regulators, which induced the production of sMER and interfered with the efferocytosis process.
肥胖症预计会通过 ADAM17 介导的 MER 酪氨酸激酶受体裂解，产生可溶性 MER（sMER），从而破坏 MERTK 与细胞死亡标志物的结合，从而阻碍吞噬作用。然而，中心性肥胖中的细胞内吞噬作用途径仍然难以捉摸，特别是在其启动和鉴定破坏吞噬作用的结合信号方面，低水平的慢性炎症的作用。
我们研究了中心性肥胖男性的吞噬作用信号通路及其与炎症、细胞死亡和相关过程的关系。
进行了一项横断面研究，从 56 名中心性肥胖男性（肥胖组）和 29 名非肥胖个体（对照组）中收集了临床数据和血液样本。进行了临床评估和预设的生化筛选测试。通过测量磷脂酰丝氨酸（PS）、ADAM17、肿瘤坏死因子-α（TNF-α）和 sMER 来研究吞噬作用信号通路。
根据预设的测试，肥胖组中超过一半的参与者检测出代谢综合征。PS、TNF-α 和 sMER 的平均水平在肥胖组中较高，但与对照组无显著差异。根据肥胖组的腰围（WC）范围进行的进一步分析显示，WC 大于 120cm 的肥胖组与对照组之间 PS 和 sMER 水平显著升高。肥胖组 ADAM17 水平明显高于对照组。PS 与 WC 和 ADAM17 呈正相关。ADAM17 与 TNF-α 和 sMER 呈正相关，表明吞噬作用受损。
中心性肥胖似乎导致吞噬作用紊乱，这种紊乱始于细胞损伤和死亡，同时 WC 增大和持续的炎症反应。吞噬作用受到促炎细胞因子调节剂的破坏，这些调节剂诱导 sMER 的产生并干扰吞噬作用过程。
