White adipose tissue-infiltrated CD11b+ myeloid cells are a source of S100A4, a new potential marker of hepatic damage

Abstract

Context 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 has been reported to be elevated in obesity and to have a role in adipose tissue dysfunction. However, the cellular source in adipose tissue and its potential role in hepatic damage in obesity has not been elucidated. Objective 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. Design 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. Results S100A4 gene expression was strongly upregulated in sWAT- vs. vWAT-infiltrated CD11b+ cells, but this modulation was not observed in T resident cells. S100A4 mRNA levels from sWAT (and not from vWAT) CD11b+ cells positively correlated with glycemia, triglycerides and TNF-α gene expression. Finally, circulating S100A4 directly correlated with liver steatosis and hepatic inflammatory markers. Conclusion 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.