Similarly, both inhibitors were able to modulate ER stress induced by the intracellular overaccumulation of FFAs, as evidenced by the down-regulation in the expression of ER stress-related transcripts and the reduction in spliced xbp1. ER-stress response and PTP1B expression are known to be closely interlinked; it has been shown that the downregulation of PTP1B expression in the liver can relieve overactivation of the ER-stress response associated with HFD feeding, obesity and insulin resistance [36]. Here, PTPN1 is linked to obesity due to melanocortin 4 receptor deficiency.