Differential regulation of the unfolded protein response in outbred deer mice and susceptibility to metabolic disease.

ABSTRACT: Endoplasmic reticulum (ER) stress has been causatively linked to the onset of various pathologies. However, whether and how inherent variations in the resulting unfolded protein response (UPR) affect predisposition to ER-stress-associated metabolic conditions remains to be established. By using genetically diverse deer mice (Peromyscus maniculatus) as a model, we show that the profile of tunicamycin-induced UPR in fibroblasts isolated at puberty varies between individuals and predicts deregulation of lipid metabolism and diet-induced hepatic steatosis later in life. Among the different UPR targets tested, CHOP (also known as Ddit3) more consistently predicted elevated plasma cholesterol and hepatic steatosis. Compared with baseline levels or inducibility, the maximal i

SUBMITTER: Havighorst A 

PROVIDER: S-EPMC6398494 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature