期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 4, 页码 1418-1423出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0607696104
关键词
mitochondrial biogenesis; oxidative metabolism; brown adipose tissue
资金
- NIDDK NIH HHS [R01 DK064951, R21 DK074660, DK064951, DK074660] Funding Source: Medline
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 alpha (ERR alpha) was the first orphan nuclear receptor to be identified, and yet its physiologic function remains unknown. Here, we show that mice lacking ERR alpha 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 ERR alpha is needed for the high levels of mitochondrial biogenesis and oxidative capacity characteristic of brown adipose tissue (BAT), and thus for providing the energy necessary for thermogenesis. ERR alpha 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 ERR alpha is a key regulator of mitochondrial biogenesis and oxidative metabolism, and essential for adaptive thermogenesis.
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