Under metabolic syndrome condition, accumulation of unfolded or misfolded proteins in the ER lumen induce the Bip protein to dissociate and bind to these proteins and subsequently activates the ER transmembrane sensors such as IRE1α, PERK/EIF2α and ATF6 through UPR signaling cascade, contributing to cells apoptosis and ER stress by ultimately initiate CHOP (ER stress-related apoptosis) [38, 39]. Here, ATF6 is linked to metabolic syndrome.