2. Academic Validation
  3. Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice

Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice

  • Nat Commun. 2023 Mar 18;14(1):1521. doi: 10.1038/s41467-023-37247-9.
Yanhao Chen # 1,  Lanlan Chen # 2,  Xiaoshan Wu # 2 3,  Yongxu Zhao 2,  Yuchen Wang 2,  Dacheng Jiang 2,  Xiaojian Liu 2,  Tingting Zhou 2,  Shuang Li 2,  Yuda Wei 4,  Yan Liu 2,  Cheng Hu 5,  Ben Zhou 2,  Jun Qin 6,  Hao Ying 2,  Qiurong Ding 7 8
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China. chenyanhao@sinh.ac.cn.
  • 2 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • 3 School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, P. R. China.
  • 4 Department of Clinical Laboratory, Linyi People's Hospital, Xuzhou Medical University, Xuzhou, Shandong, 276000, P. R. China.
  • 5 Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
  • 6 CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China.
  • 7 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China. qrding@sinh.ac.cn.
  • 8 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101, Beijing, P. R. China. qrding@sinh.ac.cn.
  • # Contributed equally.
PMID: 36934083 DOI: 10.1038/s41467-023-37247-9
Abstract

The early phase lipid accumulation is essential for liver regeneration. However, whether this acute lipid accumulation can serve as signals to direct liver regeneration rather than simply providing building blocks for cell proliferation remains unclear. Through in vivo CRISPR screening, we identify MIER1 (mesoderm induction early response 1) as a key epigenetic regulator that bridges the acute lipid accumulation and cell cycle gene expression during liver regeneration in male Animals. Physiologically, liver acute lipid accumulation induces the phosphorylation of EIF2S1(eukaryotic translation initiation factor 2), which consequently attenuated Mier1 translation. MIER1 downregulation in turn promotes cell cycle gene expression and regeneration through chromatin remodeling. Importantly, the lipids-EIF2S1-MIER1 pathway is impaired in Animals with chronic liver steatosis; whereas MIER1 depletion significantly improves regeneration in these Animals. Taken together, our studies identify an epigenetic mechanism by which the early phase lipid redistribution from adipose tissue to liver during regeneration impacts hepatocyte proliferation, and suggest a potential strategy to boost liver regeneration.

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