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

Jing Wu, Dandan Bu, Haiquan Wang, Di Shen, Danyang Chong, Tongyu Zhang, Weiwei Tao, Mengfei Zhao, Yue Zhao, Lei Fang, Peng Li (), Bin Xue () and Chao-Jun Li ()
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Jing Wu: Nanjing 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

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36775-8

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