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The rhythmic coupling of Egr-1 and Cidea regulates age-related metabolic dysfunction in the liver of male mice

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  • Jing Wu

    (Nanjing University
    Nanjing Medical University
    Nanjing Medical University)

  • Dandan Bu

    (Nanjing University)

  • Haiquan Wang

    (Nanjing University)

  • Di Shen

    (Nanjing University)

  • Danyang Chong

    (Nanjing University)

  • Tongyu Zhang

    (Nanjing University)

  • Weiwei Tao

    (Nanjing Medical University)

  • Mengfei Zhao

    (Nanjing University)

  • Yue Zhao

    (Nanjing University)

  • Lei Fang

    (Nanjing University)

  • Peng Li

    (Fudan University)

  • Bin Xue

    (Nanjing Medical University)

  • Chao-Jun Li

    (Nanjing Medical University)

Abstract

The liver lipid metabolism of older individuals canbecome impaired and the circadian rhythm of genes involved in lipid metabolism is also disturbed. Although the link between metabolism and circadian rhythms is already recognized, how these processes are decoupled in liver during aging is still largely unknown. Here, we show that the circadian rhythm for the transcription factor Egr-1 expression is shifted forward with age in male mice. Egr-1 deletion accelerates liver age-related metabolic dysfunction, which associates with increased triglyceride accumulation, disruption of the opposite rhythmic coupling of Egr-1 and Cidea (Cell Death Inducing DFFA Like Effector A) at the transcriptional level and large lipid droplet formation. Importantly, adjustment of the central clock with light via a 4-hour forward shift in 6-month-old mice, leads to recovery the rhythm shift of Egr-1 during aging and largely ameliorated liver metabolic dysfunction. All our collected data suggest that liver Egr-1 might integrate the central and peripheral rhythms and regulate metabolic homeostasis in the liver.

Suggested Citation

  • Jing Wu & Dandan Bu & Haiquan Wang & Di Shen & Danyang Chong & Tongyu Zhang & Weiwei Tao & Mengfei Zhao & Yue Zhao & Lei Fang & Peng Li & Bin Xue & Chao-Jun Li, 2023. "The rhythmic coupling of Egr-1 and Cidea regulates age-related metabolic dysfunction in the liver of male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36775-8
    DOI: 10.1038/s41467-023-36775-8
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    1. Kyeongkyu Kim & Kyungjin Boo & Young Suk Yu & Se Kyu Oh & Hyunkyung Kim & Yoon Jeon & Jinhyuk Bhin & Daehee Hwang & Keun Il Kim & Jun-Su Lee & Seung-Soon Im & Seul Gi Yoon & Il Yong Kim & Je Kyung Seo, 2017. "RORĪ± controls hepatic lipid homeostasis via negative regulation of PPARĪ³ transcriptional network," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
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