Tajbakhsh Amir, Gheibihayat Seyed Mohammad, Karami Neda, Savardashtaki Amir, Butler Alexandra E, Rizzo Manfredi, Sahebkar Amirhossein
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Medical Biotechnology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Obes Rev. 2022 Oct;23(10):e13487. doi: 10.1111/obr.13487. Epub 2022 Jun 29.
Obesity is associated with changes in the resolution of acute inflammation that contribute to the clinical complications. The exact mechanisms underlying unresolved inflammation in obesity are not fully understood. Adipocyte death leads to pro-inflammatory adipose tissue macrophages, stimulating additional adipocyte apoptosis. Thus, a complex and tightly regulated process to inhibit inflammation and maintain homeostasis after adipocyte apoptosis is needed to maintain health. In normal condition, a specialized phagocytic process (efferocytosis) performs this function, clearing necrotic and apoptotic cells (ACs) and controlling inflammation. For efficient and continued efferocytosis, phagocytes must internalize multiple ACs in physiological conditions and handle the excess metabolic burden in adipose tissue. In obesity, this control is lost and can be an important hallmark of the disease. In this regard, the deficiency of efferocytosis leads to delayed resolution of acute inflammation and can result in ongoing inflammation, immune system dysfunction, and insulin resistance in obesity. Hence, efficient clearance of ACs by M2 macrophages could limit long-term inflammation and ensue clinical complications, such as cardiovascular disease and diabetes. This review elaborates upon the molecular mechanisms to identify efferocytosis regulators in obesity, and the mechanisms that can improve efferocytosis and reduce obesity-related complications, such as the use of pharmacological agents and regular exercise.
肥胖与急性炎症消退的变化有关，这些变化会导致临床并发症。肥胖中炎症持续不消退的具体机制尚未完全明确。脂肪细胞死亡会导致促炎性脂肪组织巨噬细胞增多，进而刺激更多脂肪细胞凋亡。因此，需要一个复杂且严格调控的过程来抑制炎症，并在脂肪细胞凋亡后维持体内平衡以保持健康。在正常情况下，一种特殊的吞噬过程（凋亡细胞清除）执行此功能，清除坏死和凋亡细胞（ACs）并控制炎症。为了高效且持续地进行凋亡细胞清除，吞噬细胞必须在生理条件下内化多个ACs，并应对脂肪组织中过多的代谢负担。在肥胖状态下，这种控制机制丧失，这可能是该疾病的一个重要特征。在这方面，凋亡细胞清除功能的缺陷会导致急性炎症消退延迟，并可能在肥胖中引发持续炎症、免疫系统功能障碍和胰岛素抵抗。因此，M2巨噬细胞对ACs的有效清除可以限制长期炎症，并避免诸如心血管疾病和糖尿病等临床并发症。本综述阐述了识别肥胖中凋亡细胞清除调节因子的分子机制，以及可改善凋亡细胞清除并减少肥胖相关并发症的机制，如使用药物制剂和定期锻炼。
