肥胖和相关疾病已达到流行病的比例并继续上升。除了造成经济负担之外,肥胖及其合并症与人类预期寿命缩短有关.尽管取得了重大进展,肥胖的潜在机制仍未完全阐明.最近,几项研究强调了肥胖中各种免疫细胞的代谢重编程,从而深刻影响免疫系统。这揭示了一个新的兴趣领域:肥胖相关的全身代谢变化影响免疫系统的影响,这可能导致免疫监视丧失。在肥胖改变的免疫细胞中,不变的自然杀伤T(iNKT)细胞最近由于其识别脂质抗原的能力而获得了强烈的关注。虽然iNKT细胞被充分描述为受肥胖影响,免疫代谢因子如何以及在多大程度上(例如,脂质,葡萄糖,细胞因子,脂肪因子,胰岛素和游离脂肪酸)可以驱动iNKT细胞改变尚不清楚,但代表了一个新兴的研究领域。这里,我们回顾了目前关于肥胖中iNKT细胞的知识,并讨论了可以调节其表型和活性的免疫代谢因子。缩写:αGC,α-半乳糖神经酰胺;AMPK,AMP激活的蛋白激酶;APC,抗原呈递细胞;ApoE,载脂蛋白E;AT,脂肪组织;自动取款机,AT-巨噬细胞;BMI,体重指数;DC,树突状细胞;E4BP4,E4结合蛋白4;ER,内质网;FA,脂肪酸;FFA,游离脂肪酸;HDL,高密度脂蛋白;HFD,高脂饮食;IFN-γ,干扰素γ;IL,白细胞介素;iNKT,不变自然杀手T;IRE1α,需要肌醇的酶1α;LDL,低密度脂蛋白;LDLR,LDL受体;MHC,主要组织相容性复合体类;NK,自然杀手;PBMC,外周血单个核细胞;PERK,蛋白激酶RNA样内质网激酶;PLZF,早幼粒细胞白血病锌指;SFAs,饱和脂肪酸;TCR,T细胞受体;TNF-α,肿瘤坏死因子-α;UPR,未折叠蛋白反应;VLDL,极低密度脂蛋白.
Obesity and related diseases have reached epidemic proportions and continue to rise. Beyond creating an economical burden, obesity and its co-morbidities are associated with shortened human life expectancy. Despite major advances, the underlying mechanisms of obesity remain not fully elucidated. Recently, several studies have highlighted that various immune cells are metabolically reprogrammed in obesity, thereby profoundly affecting the immune system. This sheds light on a new field of interest: the impact of obesity-related systemic metabolic changes affecting immune system that could lead to immunosurveillance loss. Among immune cells altered by obesity, invariant Natural Killer T (iNKT) cells have recently garnered intense focus due to their ability to recognize lipid antigen. While iNKT cells are well-described to be affected by obesity, how and to what extent immunometabolic factors (e.g., lipids, glucose, cytokines, adipokines, insulin and free fatty acids) can drive iNKT cells alterations remains unclear, but represent an emerging field of research. Here, we review the current knowledge on iNKT cells in obesity and discuss the immunometabolic factors that could modulate their phenotype and activity.