Department of Physiology, Institute of Neuroscience Research, Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, University of South China, Hengyang, Hunan 421001, P.R. China.
Institute of Cardiovascular Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511500, P.R. China.
Mol Med Rep. 2023 Dec;28(6). doi: 10.3892/mmr.2023.13121. Epub 2023 Nov 3.
Insulin growth factor‑1 (IGF‑1) is an endocrine regulator that plays an important role in normal growth and development. IGF‑1 mediated effects may result in protecting macrophages from immunometabolic response. However, it is unclear whether IGF‑1 has a protective effect on fatty acid‑induced macrophages damage. In the present study, THP‑1 cells were differentiated into macrophages and stimulated with palmitic acid (PA) in the absence or presence of IGF‑1. Macrophages apoptosis was measured by Cell Counting Kit‑8 assay, flow cytometry, Hoechst 33342 staining and western blotting. The mitochondrial damage was evaluated using JC‑1 staining and mitochondrial reactive oxygen species detection. The activation of mitophagy was assessed using immunofluorescence and western blotting. As a result, IGF‑1 significantly restored the survival rate in macrophages, while the apoptosis was inhibited through mitochondrial pathway. In addition, IGF‑1 protected the mitochondrial damage induced by PA. Furthermore, PA induced mitophagy via phosphatase and tensin homolog‑induced putative kinase protein 1/Parkin, which was reversed by IGF‑1. Taken together, the present study demonstrated the protective effect of IGF‑1 on PA‑induced mitochondrial apoptosis in macrophages, which might provide a potential therapeutic strategy for treatment of lipotoxicity.
胰岛素样生长因子 1（IGF-1）是一种内分泌调节剂，在正常生长和发育中发挥重要作用。IGF-1 介导的作用可能导致巨噬细胞免受免疫代谢反应的影响。然而，目前尚不清楚 IGF-1 是否对脂肪酸诱导的巨噬细胞损伤具有保护作用。在本研究中，将 THP-1 细胞分化为巨噬细胞，并在存在或不存在 IGF-1 的情况下用棕榈酸（PA）刺激。通过细胞计数试剂盒-8 测定法、流式细胞术、Hoechst 33342 染色和蛋白质印迹法测量巨噬细胞凋亡。使用 JC-1 染色和线粒体活性氧检测评估线粒体损伤。通过免疫荧光和蛋白质印迹法评估自噬的激活。结果表明，IGF-1 可显著恢复巨噬细胞的存活率，同时通过线粒体途径抑制细胞凋亡。此外，IGF-1 可保护 PA 诱导的线粒体损伤。此外，PA 通过磷酸酶和张力蛋白同源物诱导的假定激酶蛋白 1/ Parkin 诱导自噬，IGF-1 可逆转这一过程。综上所述，本研究表明 IGF-1 对 PA 诱导的巨噬细胞线粒体凋亡具有保护作用，这可能为治疗脂毒性提供一种潜在的治疗策略。
