1. Life Sciences Institute and Department of Cell & Developmental Biology
2. Department of Molecular and Integrative Physiology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA

Correspondence to: Jiandie D. Lin¹ Correspondence and requests for materials should be addressed to J.D.L. (Email: jdlin@umich.edu).

Abstract

The mammalian clock regulates major aspects of energy metabolism, including glucose and lipid homeostasis and mitochondrial oxidative metabolism^{1, 2}. The biochemical basis for coordinated control of the circadian clock and diverse metabolic pathways is not well understood. Here we show that PGC-1 (Ppargc1a), a transcriptional coactivator that regulates energy metabolism^{3, 4, 5, 6, 7, 8, 9}, is rhythmically expressed in the liver and skeletal muscle of mice. PGC-1 stimulates the expression of clock genes, notably Bmal1 (Arntl) and Rev-erb (Nr1d1), through coactivation of the ROR family of orphan nuclear receptors. Mice lacking PGC-1 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-1-deficient fibroblasts and mice with liver-specific knockdown of PGC-1 indicate that it is required for cell-autonomous clock function. We have thus identified PGC-1 as a key component of the circadian oscillator that integrates the mammalian clock and energy metabolism.

1. Life Sciences Institute and Department of Cell & Developmental Biology
2. Department of Molecular and Integrative Physiology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA

Correspondence to: Jiandie D. Lin¹ Correspondence and requests for materials should be addressed to J.D.L. (Email: jdlin@umich.edu).

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