Isolation stress for 30 days alters hepatic gene expression profiles, especially with reference to lipid metabolism in mice

Motoyama K, Nakai Y, Miyashita T, Fukui Y, Morita M, Sanmiya K, Sakakibara H, Matsumoto I, Abe K, Yakabe T, Yajima N, Shimoi K. Isolation stress for 30 days alters hepatic gene expression profiles, especially with reference to lipid metabolism in mice. Physiol Genomics 37: 79-87, 2009. First published December 23, 2008; doi: 10.1152/physiolgenomics.90358.2008.-To elucidate the physiological responses to a social stressor, we exposed mice to an isolation stress and analyzed their hepatic gene expression profiles using a DNA microarray. Male BALB/c mice were exposed to isolation stress for 30 days, and then hepatic RNA was sampled and subjected to DNA microarray analysis. The isolation stress altered the expression of 420 genes (after considering the false discovery rate). Gene Ontology analysis of these differentially expressed genes indicated that the stress remarkably downregulated the lipid metabolism-related pathway through peroxisome proliferator-activated receptor-alpha, while the lipid biosynthesis pathway controlled by sterol regulatory element binding factor 1, Golgi vesicle transport, and secretory pathway-related genes were significantly upregulated. These results suggest that isolation for 30 days with a mild and consecutive social stress regulates the systems for lipid metabolism and also causes endoplasmic reticulum stress in mouse liver.