Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism
The mammalian clock regulates major aspects of energy metabol-ism, including glucose and lipid homeostasis and mitochondrial oxidative metabolism1,2. The biochemical basis for coordinated control of the circadian clock and diverse metabolic pathways is not well understood. Here we show that PGC-lα (Ppargcla), a transcriptional coactivator that regulates energy metabolism3-9,is rhythmically expressed in the liver and skeletal muscle of mice.PGC-la stimulates the expression of clock genes, notably Bmall (Arntl) and Rev-erba (Nrldl), through coactivation of the ROR family of orphan nuclear receptors. Mice lacking PGC-la show abnormal diurnal rhythms of activity, body temperature and metabolic rate. The disruption of physiological rhythms in these animals is correlated with aberrant expression of clock genes and those involved in energy metabolism. Analyses of PGC- la-deficient fibroblasts and mice with liver-specific knockdown of PGC-la indicate that it is required for cell-autonomous clock function. We have thus identified PGC-la as a key component of the circadian oscillator that integrates the mammalian clock and energy metabolism.
Chang Liu Siming Li Tiecheng Liu Jimo Borjigin Jiandie D.Lin
Life Sciences Institute and Department of Cell & Developmental Biology Department of Molecular and Integrative Physiology, University of Michigan Medical Center, Ann Arbor
国际会议
南京
英文
107-111
2009-09-11（万方平台首次上网日期，不代表论文的发表时间）