TY - JOUR
T1 - Orphan nuclear receptor estrogen-related receptor α is essential for adaptive themogenesis
AU - Villena, Josep A.
AU - Hock, M. Benjamin
AU - Chang, William Y.
AU - Barcas, Joanalyn E.
AU - Giguère, Vincent
AU - Kralli, Anastasia
PY - 2007/1/23
Y1 - 2007/1/23
N2 - Survival of organisms requires the ability to adapt to changes in the environment. Adaptation of oxidative metabolism is essential for meeting increased energy demands in response to Stressors, such as exposure to cold temperatures or increased physical activity. Adaptive changes in metabolism are often achieved at the level of gene expression, and nuclear receptors have prevalent roles in mediating such responses. Estrogen-related receptor α(ERRα) was the first orphan nuclear receptor to be identified, and yet its physiologic function remains unknown. Mere, we show that mice lacking ERRα are unable to maintain body temperature when exposed to cold. Surprisingly, the inability to adapt to cold is not due to defects in the acute transcriptional induction of genes important for thermogenesis. Rather, we show that ERRα is needed for the high levels of mitochondria! biogenesis and oxidative capacity characteristic of brown adipose tissue (BAT), and thus for providing the energy necessary for thermogenesis. ERRa fulfills this role by acting directly at genes important for mitochondrial function, parallel to other factors controlling mitochondrial gene expression, such as NRF1 and NRF2/GABPA. Our findings demonstrate that ERRα is a key regulator of mitochondrial biogenesis and oxidative metabolism, and essential for adaptive thermogenesis.
AB - Survival of organisms requires the ability to adapt to changes in the environment. Adaptation of oxidative metabolism is essential for meeting increased energy demands in response to Stressors, such as exposure to cold temperatures or increased physical activity. Adaptive changes in metabolism are often achieved at the level of gene expression, and nuclear receptors have prevalent roles in mediating such responses. Estrogen-related receptor α(ERRα) was the first orphan nuclear receptor to be identified, and yet its physiologic function remains unknown. Mere, we show that mice lacking ERRα are unable to maintain body temperature when exposed to cold. Surprisingly, the inability to adapt to cold is not due to defects in the acute transcriptional induction of genes important for thermogenesis. Rather, we show that ERRα is needed for the high levels of mitochondria! biogenesis and oxidative capacity characteristic of brown adipose tissue (BAT), and thus for providing the energy necessary for thermogenesis. ERRa fulfills this role by acting directly at genes important for mitochondrial function, parallel to other factors controlling mitochondrial gene expression, such as NRF1 and NRF2/GABPA. Our findings demonstrate that ERRα is a key regulator of mitochondrial biogenesis and oxidative metabolism, and essential for adaptive thermogenesis.
KW - Brown adipose tissue
KW - Mitochondrial biogenesis
KW - Oxidative metabolism
UR - http://www.scopus.com/inward/record.url?scp=33846604723&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846604723&partnerID=8YFLogxK
U2 - 10.1073/pnas.0607696104
DO - 10.1073/pnas.0607696104
M3 - Article
C2 - 17229846
AN - SCOPUS:33846604723
SN - 0027-8424
VL - 104
SP - 1418
EP - 1423
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -