Son Kuk Hui, Son Myeongjoo, Ahn Hyosang, Oh Seyeon, Yum Yoonji, Choi Chang Hu, Park Kook Yang, Byun Kyunghee
Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon, Republic of Korea.
Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon, Republic of Korea; Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.
Biochem Biophys Res Commun. 2016 Aug 19;477(2):271-6. doi: 10.1016/j.bbrc.2016.06.056. Epub 2016 Jun 11.
Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly.
与皮下脂肪相比，内脏脂肪通过激活巨噬细胞诱导更多炎症，而炎症是包括心血管疾病和糖尿病在内的各种疾病发病机制的一个潜在特征。晚期糖基化终产物（AGEs）、S100β及其受体，即晚期糖基化终产物受体（RAGE），会导致巨噬细胞激活。然而，关于脂肪组织中不同脂肪细胞类型中AGE修饰白蛋白（由AGEs修饰的血清白蛋白）、S100β的差异积累或RAGE表达的信息却很少。在本研究中，作者调查了与年龄相关的AGE修饰白蛋白积累、S100β水平以及RAGE表达在皮下和内脏脂肪组织中是否存在差异。从3周龄和28周龄大鼠中采集皮下和内脏脂肪。通过Iba1染色确认巨噬细胞激活，并通过共聚焦显微镜评估AGE修饰白蛋白积累和RAGE表达。通过免疫印迹分析S100β。研究发现，28周龄大鼠内脏脂肪中活化的巨噬细胞浸润、AGE修饰白蛋白积累和S100β明显高于3周龄大鼠，但皮下脂肪中的情况相似。28周龄大鼠内脏脂肪中RAGE的表达明显更高，但3周龄和28周龄大鼠皮下脂肪中RAGE的表达相似。此外，28周龄大鼠内脏脂肪中的炎症信号通路（NFκB、TNF-α）和增殖通路（FAK）更活跃。这些结果表明，与年龄相关的AGE修饰白蛋白积累、S100β和RAGE表达在内脏脂肪中比在皮下脂肪中更显著，这表明内脏脂肪参与了老年人炎症诱导疾病的发病机制。
