Stressed out about obesity: IRE1α-XBP1 in metabolic disorders

The global obesity epidemic is associated with a series of health-threatening diseases including type 2 diabetes. Accumulating evidence suggest that the physiology and homeostasis of the endoplasmic reticulum (ER) is intimately involved in the underlying mechanisms linking obesity and diabetes. Specifically, recent studies indicate a crucial role for the inositol-requiring enzyme 1 alpha (IRE1 alpha)/X-box binding protein 1 (XBP1) pathway, the most conserved branch of the unfolded protein response (UPR), in glucose and lipid metabolism as well as in insulin function. Focusing on the IRE1 alpha-XBP1 pathway, we review recent advances in our understanding of the role of UPR in obesity and obesity-associated metabolic disorders.