Thy1 (CD90) expression is regulated by DNA methylation during adipogenesis

Abstract

The obesity epidemic is developing into the most costly health problem facing the world. Obesity, characterized by excessive adipogenesis and enlarged adipocytes, promotes morbidities, such as diabetes, cardiovascular disease, and cancer. Regulation of adipogenesis is critical to our understanding of how fat cell formation causes obesity and associated health problems. Thy1 (also called CD90), a widely used stem cell marker, blocks adipogenesis and reduces lipid accumulation. Thy1‐knockout mice are prone to diet‐induced obesity. Although the importance of Thy1 in adipogenesis and obesity is now evident, how its expression is regulated is not. We hypothesized that DNA methylation has a role in promoting adipogenesis and affects Thy1 expression. Using the methylation inhibitor 5‐aza‐2 ‐deoxycytidine (5‐aza‐dC), we investigated whether DNA methylation alters Thy1 expression during adipogenesis in both mouse 3T3‐L1 preadipocytes and mouse mesenchymal stem cells. Thy1 protein and mRNA levels were decreased dramatically during adipogenesis. However, 5‐aza‐dC treatment prevented that phenomenon. Methylation‐sensitive pyrosequencing analysis showed that CpG sites at the Thy1 locus have increased methylation during adipogenesis, as well as increased methylation in adipose tissue from diet‐induced obese mice. These new findings highlight the potential role of Thy1 and DNA methylation in adipogenesis and obesity.—Flores, E. M., Woeller, C. F., Falsetta, M. L., Susiarjo, M., Phipps, R. P. Thy1 (CD90) expression is regulated by DNA methylation during adipogenesis. FASEB J. 33, 3353–3363 (2019). www.fasebj.org