Leinweber Brinja, Pilorz Violetta, Olejniczak Iwona, Skrum Ludmila, Begemann Kimberly, Heyde Isabel, Stenger Sarah, Sadik Christian David, Oster Henrik
University of Lübeck, Institute of Neurobiology, Center of Brain, Behaviour and Metabolism, Marie-Curie-Strasse, 23562 Luebeck, Germany.
University of Lübeck, Department of Dermatology, Allergy, and Venereology Ratzeburger Allee, 23562 Luebeck, Germany.
iScience. 2025 Feb 25;28(3):112038. doi: 10.1016/j.isci.2025.112038. eCollection 2025 Mar 21.
Physiological processes, including metabolism and immune responses, are generated by the circadian clock, driven by clock genes. Disrupting circadian rhythms through a high-fat diet promotes obesity and inflammation. Studies show that deleting the clock gene, brain, and muscle ARNT-like 1 () in adipose tissue leads to overeating and weight gain. We now show that deletion in neutrophils protects against diet-induced obesity and reduces inflammatory macrophage infiltration into epididymal white adipose tissue (eWAT), despite increased food intake over 20 weeks of a high-fat diet. This protection is linked to enhanced energy expenditure, increased UCP1 expression in iBAT, improved insulin sensitivity, and altered expression of genes encoding chemokine receptors CXCR2, CXCR4, and the ligand Cxcl2 in eWAT. Our findings reveal a key role of in neutrophils in regulating high-fat diet-induced adipose inflammation and emphasize circadian regulation's importance in immuno-metabolic function.
包括新陈代谢和免疫反应在内的生理过程是由生物钟产生的，生物钟由时钟基因驱动。通过高脂饮食扰乱昼夜节律会促进肥胖和炎症。研究表明，在脂肪组织中删除时钟基因脑和肌肉芳香烃受体核转位蛋白样蛋白1（）会导致暴饮暴食和体重增加。我们现在表明，尽管在高脂饮食的20周内食物摄入量增加，但中性粒细胞中的缺失可预防饮食诱导的肥胖，并减少炎症性巨噬细胞浸润到附睾白色脂肪组织（eWAT）中。这种保护作用与能量消耗增加、iBAT中UCP1表达增加、胰岛素敏感性改善以及eWAT中编码趋化因子受体CXCR2、CXCR4和配体Cxcl2的基因表达改变有关。我们的研究结果揭示了中性粒细胞中的在调节高脂饮食诱导的脂肪炎症中的关键作用，并强调了昼夜节律调节在免疫代谢功能中的重要性。
