P2RX7 and obesity due to melanocortin 4 receptor deficiency: However, given the “double-edged sword” nature of P2X7 (136), caution must still be recommended because continuous or excessive stimulation of P2X7 could exacerbate endoplasmic reticulum stress that has been recently recognized to be mechanistically involved in the decrease of brown AT-dependent EE and obesity progression (137).