Lee Sella, Kim Hye-Kyeong
Department of Food Science and Nutrition, The Catholic University of Korea, Bucheon 14662, Korea.
Nutr Res Pract. 2024 Dec;18(6):761-773. doi: 10.4162/nrp.2024.18.6.761. Epub 2024 Aug 14.
BACKGROUND/OBJECTIVES: The infiltration of macrophages into adipose tissue mediates chronic inflammation that is associated with insulin resistance in obesity. Although vitamin E is beneficial against insulin resistance, its impact on adipose tissue inflammation has not been elucidated. This study aims to investigate the effects of α-tocopherol and γ-tocopherol, major vitamin E isoforms, on the interaction between macrophages and adipocytes with regard to obesity-induced inflammation and insulin resistance.
MATERIALS/METHODS: Hypertrophied 3T3-L1 adipocytes were cocultured with RAW 264.7 macrophages and treated with α-tocopherol or γ-tocopherol at 12.5, 25, and 50 µM. The inflammatory cytokines (monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6) and free fatty acid (FFA) release were measured by assay kits, and nuclear factor-kappaB (NF-κB) and c-Jun NH terminal kinase (JNK) signals were evaluated by immunoblotting. Glucose uptake was measured with a fluorescent glucose derivative.
Treatment with α-tocopherol and γ-tocopherol restrained the coculture-induced increase in cytokines and FFA release. γ-Tocopherol exhibited greater suppression of inflammatory cytokines at 12.5 and 25 µM ( < 0.001). Both tocopherols inhibited NF-κB activation by limiting translocation of NF-κB (p65) to the nucleus, with γ-tocopherol showing a stronger effect compared to α-tocopherol. α-Tocopherol inhibited JNK phosphorylation at 50 μM, whereas γ-tocopherol did not. Furthermore, coculture with macrophages impaired glucose uptake in response to insulin, but both tocopherols restored insulin responsiveness ( < 0.01).
α-Tocopherol and γ-tocopherol effectively mitigate inflammation induced by adipocyte-macrophage interaction, thereby ameliorating coculture-induced insulin resistance. These findings suggest the therapeutic potential of tocopherols in managing obesity-related metabolic dysfunction.
背景/目的：巨噬细胞浸润至脂肪组织会介导慢性炎症，而这种炎症与肥胖中的胰岛素抵抗相关。尽管维生素E对胰岛素抵抗有益，但其对脂肪组织炎症的影响尚未阐明。本研究旨在探究主要的维生素E异构体α-生育酚和γ-生育酚，在肥胖诱导的炎症和胰岛素抵抗方面，对巨噬细胞与脂肪细胞之间相互作用的影响。
材料/方法：将肥大的3T3-L1脂肪细胞与RAW 264.7巨噬细胞共培养，并用12.5、25和50μM的α-生育酚或γ-生育酚进行处理。通过检测试剂盒测定炎性细胞因子（单核细胞趋化蛋白-1、肿瘤坏死因子-α和白细胞介素-6）和游离脂肪酸（FFA）释放量，并通过免疫印迹法评估核因子-κB（NF-κB）和c-Jun氨基末端激酶（JNK）信号。用荧光葡萄糖衍生物测量葡萄糖摄取。
用α-生育酚和γ-生育酚处理可抑制共培养诱导的细胞因子增加和FFA释放。γ-生育酚在12.5和25μM时对炎性细胞因子的抑制作用更强（<0.001）。两种生育酚均通过限制NF-κB（p65）向细胞核的转位来抑制NF-κB活化，与α-生育酚相比，γ-生育酚的作用更强。α-生育酚在50μM时抑制JNK磷酸化，而γ-生育酚则无此作用。此外，与巨噬细胞共培养会损害胰岛素刺激的葡萄糖摄取，但两种生育酚均可恢复胰岛素反应性（<0.01）。
α-生育酚和γ-生育酚可有效减轻脂肪细胞-巨噬细胞相互作用诱导的炎症，从而改善共培养诱导的胰岛素抵抗。这些发现表明生育酚在管理肥胖相关代谢功能障碍方面具有治疗潜力。
