肥胖是世界范围内日益严重的问题，也是许多慢性病的主要危险因素。脂肪组织的积累导致大量促炎细胞因子和脂肪因子的释放，导致低度全身炎症。然而，肥胖相关疾病发生背后的机制尚不完全清楚。因此，我们的研究旨在探讨两种不同饮食诱导的小鼠肥胖模型中全身水平和个体器官的病理变化和炎症过程。雄性C57BL6/J小鼠采用高脂饮食（HFD）、高脂/从 3 月龄开始，高果糖饮食 (HFD   FR) 或正常饮食 21 周（n = 15 只动物/组）。通过口服葡萄糖耐量试验来检测胰岛素抵抗。用苏木精-伊红染色的肝脏和棕色脂肪组织切片研究病理变化。通过 qPCR 分析脂肪组织中脂肪因子和细胞因子的基因表达水平，而血清蛋白浓度则通过多重免疫测定法测定。采用单细胞质谱流式技术对分离的血液、骨髓和脾细胞进行免疫表型分析。HFD  FR组的体重增加、葡萄糖耐受不良和肝脏脂肪变性比对照组和HFD组更严重。这伴随着更高水平的全身炎症，如内脏白色脂肪组织中促炎基因表达增加和血清 TNFα 水平升高所表明的。此外，免疫表型分析显示，肥胖动物中各种细胞类型（例如 CD8 和 CD4  T 细胞、B 细胞和巨噬细胞）上 CD44 和 CD69 的表面表达增加。 HFD 与果糖补充相结合可更有效地促进代谢综合征的症状。因此，高脂/高果糖联合营养可能是更适合西方饮食的模式。然而，尽管存在这些差异，两种模型都显示出可能与肥胖相关癌症风险增加相关的免疫表型变化。© 2024。作者。

Obesity is a growing problem worldwide and a major risk factor for many chronic diseases. The accumulation of adipose tissue leads to the release of significant amounts of pro-inflammatory cytokines and adipokines, resulting in a low-grade systemic inflammation. However, the mechanisms behind the development of obesity-related diseases are not fully understood. Therefore, our study aimed to investigate the pathological changes and inflammatory processes at systemic level and in individual organs in two different diet-induced mouse obesity models.Male C57BL6/J mice were fed by high-fat diet (HFD), high-fat/high-fructose diet (HFD + FR) or normal chow for 21 weeks starting at 3 months of age (n = 15 animals/group). Insulin resistance was tested by oral glucose tolerance test. Pathological changes were investigated on hematoxylin-eosin-stained liver and brown adipose tissue sections. The gene expression levels of adipokines and cytokines were analyzed by qPCR in adipose tissues, whereas serum protein concentrations were determined by multiplex immunoassays. Immunophenotyping of isolated blood, bone marrow and spleen cells was performed by single-cell mass cytometry.Weight gain, glucose intolerance and hepatic steatosis were more severe in the HFD + FR group than in the control and HFD groups. This was accompanied by a higher level of systemic inflammation, as indicated by increased expression of pro-inflammatory genes in visceral white adipose tissue and by a higher serum TNFα level. In addition, immunophenotyping revealed the increase of the surface expressions of CD44 and CD69 on various cell types, such as CD8+ and CD4 + T-cells, B-cells and macrophages, in animals with obesity.The combination of HFD with fructose supplementation promotes more properly the symptoms of metabolic syndrome. Therefore, the combined high-fat/high-fructose nutrition can be a more suitable model of the Western diet. However, despite these differences, both models showed immunophenotypic changes that may be associated with increased risk of obesity-related cancer.© 2024. The Author(s).