TC-E 5003, a protein methyltransferase 1 inhibitor, activates the PKA-dependent thermogenic pathway in primary murine and human subcutaneous adipocytes

We previously reported the involvement of protein arginine methyltransferase 1 (PRMT1) in adipocyte thermogenesis. Here, we investigate the effects of PRMT1 inhibitors on thermogenesis. Unexpectedly, we find that the PRMT1 Inhibitor TC-E 5003 (TC-E) induces the thermogenic properties of primary murine and human subcutaneous adipocytes. TC-E treatment upregulates the expression of Ucp1 and Fgf21 significantly and activates protein kinase A signaling and lipolysis in primary subcutaneous adipocytes from both mouse and humans. We further find that the thermogenic effects of TC-E are independent of PRMT1 and beta-adrenergic receptors. Our data indicate that TC-E exerts strong effects on murine and human subcutaneous adipocytes by activating beige adipocytes via PKA signaling.