Department of Endocrinology and Nutrition, Germans Trias i Pujol Research Institute.
Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain.
Eur J Endocrinol. 2021 Apr;184(4):533-541. doi: 10.1530/EJE-20-1130.
The endocrine and immunological properties of subcutaneous vs visceral adipose tissue (sWAT and vWAT, respectively) have turned a milestone in the study of metabolic diseases. The cytokine S100A4 is increased in obesity and has a role in adipose tissue dysfunction. However, the cellular source and its potential role in hepatic damage in obesity has not been elucidated.
We aim to study the regulation of S100A4 in immune cells present in sWAT and vWAT, as well as its potential role as a circulating marker of hepatic inflammation and steatosis.
A cohort of 60 patients with obesity and distinct metabolic status was analyzed. CD11b+ myeloid cells and T cells were isolated from sWAT and vWAT by magnetic-activating cell sorting, and RNA was obtained. S100A4 gene expression was measured, and correlation analysis with clinical data was performed. Liver biopsies were obtained from 20 patients, and S100A4 circulating levels were measured to check the link with hepatic inflammation and steatosis.
S100A4 gene expression was strongly upregulated in sWAT- vs vWAT-infiltrated CD11b+ cells, but this modulation was not observed in T cells. S100A4 mRNA levels from sWAT (and not from vWAT) CD11b+ cells positively correlated with glycemia, triglycerides, TNF-α gene expression and proliferation markers. Finally, circulating S100A4 directly correlated with liver steatosis and hepatic inflammatory markers.
Our data suggest that sWAT-infiltrated CD11b+ cells could be a major source of S100A4 in obesity. Moreover, our correlations identify circulating S100A4 as a potential novel biomarker of hepatic damage and steatosis.
皮下和内脏脂肪组织（分别为 sWAT 和 vWAT）的内分泌和免疫特性已成为代谢性疾病研究的一个里程碑。细胞因子 S100A4 在肥胖症中增加，并且在脂肪组织功能障碍中具有作用。然而，其在肥胖症中肝损伤的细胞来源及其潜在作用尚未阐明。
我们旨在研究 sWAT 和 vWAT 中免疫细胞中 S100A4 的调节及其作为循环标志物在肝炎症和脂肪变性中的潜在作用。
对 60 例肥胖且代谢状态不同的患者进行了分析。通过磁性激活细胞分选从 sWAT 和 vWAT 中分离出 CD11b+髓样细胞和 T 细胞，并获得 RNA。测量 S100A4 基因表达，并与临床数据进行相关性分析。从 20 例患者中获得肝活检，并测量 S100A4 循环水平以检查其与肝炎症和脂肪变性的关系。
sWAT 浸润的 CD11b+细胞中 S100A4 基因表达强烈上调，但在 T 细胞中未观察到这种调节。sWAT（而非 vWAT）CD11b+细胞中的 S100A4 mRNA 水平与血糖，甘油三酸酯，TNF-α基因表达和增殖标志物呈正相关。最后，循环 S100A4 与肝脂肪变性和肝炎症标志物直接相关。
我们的数据表明，sWAT 浸润的 CD11b+细胞可能是肥胖症中 S100A4 的主要来源。此外，我们的相关性将循环 S100A4 确定为肝损伤和脂肪变性的潜在新型生物标志物。
