Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
J Immunol. 2022 Jan 1;208(1):121-132. doi: 10.4049/jimmunol.2100231. Epub 2021 Dec 6.
Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected and mice (C57BL/6J genetic background) to an 8-wk high-fat and high-sucrose diet. The total body weight was the same in and mice after diet treatment. Expression of white adipose tissue genes linked to inflammatory pathways were lower in mice. We also noted reduced total macrophage abundance, a reduced proportion of proinflammatory M1 macrophages, and reduced formation of crown-like structures in adipose tissue of compared with mice. Further, mice had more medium-sized adipocytes and fewer large adipocytes. Differentiation of preadipocytes into adipocytes (3T3-L1) was accompanied by reduced mRNA expression. In line with this, analysis of single-cell RNA sequencing data from mouse and human adipose tissue supports that mRNA is predominantly expressed by various immune cells, with low expression in adipocytes. mRNA expression was higher in obese compared with lean humans and mice, accompanied by an increased expression of immune cell gene markers. and inflammatory marker mRNA expression was reduced upon substantial weight loss in patients after bariatric surgery. Taken together, this study introduces a role for serglycin in the regulation of obesity-induced adipose inflammation.
脂肪组织的慢性局部炎症是肥胖的一个重要特征。硫酸软骨素蛋白聚糖是一种高度表达的蛋白聚糖，已知各种免疫细胞在肥胖条件下会浸润脂肪组织。为了研究硫酸软骨素蛋白聚糖的表达是否对饮食诱导的脂肪组织炎症有影响，我们让 和 （C57BL/6J 遗传背景）小鼠接受 8 周高脂肪高蔗糖饮食。饮食治疗后， 和 小鼠的总体重相同。与 小鼠相比， 小鼠白色脂肪组织中与炎症途径相关的基因表达降低。我们还注意到， 小鼠的总巨噬细胞数量减少，促炎 M1 巨噬细胞比例降低，脂肪组织中冠状结构形成减少。此外， 小鼠的中等大小脂肪细胞较多，大脂肪细胞较少。前脂肪细胞分化为脂肪细胞（3T3-L1）时， mRNA 表达减少。与此一致的是，来自小鼠和人类脂肪组织的单细胞 RNA 测序数据分析表明， mRNA 主要由各种免疫细胞表达，在脂肪细胞中的表达水平较低。与瘦小鼠相比，肥胖小鼠和人类的 mRNA 表达更高，伴随着免疫细胞基因标志物的表达增加。在减肥手术后，患者的体重显著减轻， 和炎症标志物的 mRNA 表达降低。综上所述，本研究介绍了硫酸软骨素蛋白聚糖在调节肥胖引起的脂肪组织炎症中的作用。
