Final Activity Report Summary - PGC1? IN BRAIN (Role of PGC 1? coactivator in the brain: energy homeostasis, obesity, ageing and neuronal death)
Given the fact that PGC-1ß is involved in the lipid handling under positive energy balance in liver, we wondered whether under physiological conditions the absence of this coactivator may be associated with failure in the brain lipid homeostasis. Hypothalamic gene expression of PGC-1ß KO mice showed a decrease in the gene expression related with lipid metabolism like SREBP1c, LXRbeta and RXRbeta. We wondered whether the failure in lipids handling of PGC-1ß mice may result in physiologically ER stress response. We found a significant increase in the basal XBPs and CHOP gene expression, and upregulation in the basal protein content of GRP78 and CHOP, three genes related with ER stress response. We found also that ER stress pathway activation is disturbed in PGC-1ß KO mice exposed to six months high fat diet. As in vivo, neuronal culture from PGC-1ß KO mice are insensitive to respond to pharmacologic ER stress stimulation by tunicamycin or thapsigargin, compared to WT mice. These experiments provided new information about the role of PGC-1ß in the ER stress response associated to lipid homeostasis and its role in the energy homeostasis.