TY - JOUR
T1 - PGC-1α in aging and lifelong exercise training-mediated regulation of UPR in mouse liver
AU - Maag Kristensen, Caroline
AU - Brandt, Christina Tingbjerg
AU - Jørgensen, Stine Ringholm
AU - Pilegaard, Henriette
PY - 2017/11
Y1 - 2017/11
N2 - Aging is associated with changes in several metabolic pathways affecting liver function including the adaptive unfolded protein response (UPR). On the other hand, exercise training has been shown to exert beneficial effects on metabolism in the liver and exercise training has been reported to affect hepatic UPR. PGC-1α is a transcriptional coactivator involved in exercise training-induced adaptations in skeletal muscle and liver. Therefore, the aim of the present study was to examine the impact of PGC-1α in aging and lifelong exercise training-induced hepatic UPR in mice. Liver was obtained from young (3 months old), aged (15 months old) and lifelong exercise trained aged wild-type (WT) and whole-body PGC-1α knockout (KO) mice. Hepatic BiP, IRE1α and cleaved ATF6 protein content increased, whereas PERK protein content was reduced with aging indicating both increased and decreased capacity of specific UPR pathways and increased activity of the ATF6 pathway in the liver with aging. Lifelong exercise training prevented the age-associated change in BiP and IRE1α protein, but not cleaved ATF6 protein and resulted in further decreased PERK protein. Taken together, the present study provides evidence that the capacity and activity of the three UPR pathways are differentially regulated in the liver with aging and lifelong exercise training. In addition, PGC-1α does not seem to regulate the activity of hepatic UPR in response to exercise training, but to influence the capacity of the liver to induce UPR in a pathway specific manner.
AB - Aging is associated with changes in several metabolic pathways affecting liver function including the adaptive unfolded protein response (UPR). On the other hand, exercise training has been shown to exert beneficial effects on metabolism in the liver and exercise training has been reported to affect hepatic UPR. PGC-1α is a transcriptional coactivator involved in exercise training-induced adaptations in skeletal muscle and liver. Therefore, the aim of the present study was to examine the impact of PGC-1α in aging and lifelong exercise training-induced hepatic UPR in mice. Liver was obtained from young (3 months old), aged (15 months old) and lifelong exercise trained aged wild-type (WT) and whole-body PGC-1α knockout (KO) mice. Hepatic BiP, IRE1α and cleaved ATF6 protein content increased, whereas PERK protein content was reduced with aging indicating both increased and decreased capacity of specific UPR pathways and increased activity of the ATF6 pathway in the liver with aging. Lifelong exercise training prevented the age-associated change in BiP and IRE1α protein, but not cleaved ATF6 protein and resulted in further decreased PERK protein. Taken together, the present study provides evidence that the capacity and activity of the three UPR pathways are differentially regulated in the liver with aging and lifelong exercise training. In addition, PGC-1α does not seem to regulate the activity of hepatic UPR in response to exercise training, but to influence the capacity of the liver to induce UPR in a pathway specific manner.
KW - Aging
KW - ER stress
KW - Exercise
KW - Liver
KW - PGC-1α
KW - UPR
UR - http://www.scopus.com/inward/record.url?scp=85027576451&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2017.08.006
DO - 10.1016/j.exger.2017.08.006
M3 - Journal article
C2 - 28801170
AN - SCOPUS:85027576451
SN - 0531-5565
VL - 98
SP - 124
EP - 133
JO - Experimental Gerontology
JF - Experimental Gerontology
ER -