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

Nature Communications · 16 authors, 6 centres

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The central finding is that acute lipid accumulation post-hepatectomy activates the EIF2S1 pathway, leading to translational repression of the epigenetic regulator MIER1.

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The central finding is that acute lipid accumulation post-hepatectomy activates the EIF2S1 pathway, leading to translational repression of the epigenetic regulator MIER1. The study contrasts this mechanism with chronic steatosis (from aging or high-fat diet), where hepatocytes become insensitive to acute stress, compromising MIER1 regulation and liver regeneration.

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other

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preclinical research

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ORIGINAL PAPER

PMC10024732

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

Nature Communications

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ABSTRACT

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. Subject terms: Cell proliferation, Hepatocytes

CITATION EXPORT

Yanhao Chen, Lanlan Chen, Xiaoshan Wu et al.. Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice. Nature Communications. (2023). https://doi.org/10.1038/s41467-023-37247-9

AUTHORS

16 · 6 CENTRES

Yanhao Chen, Lanlan Chen, Xiaoshan Wu, Yongxu Zhao, Yuchen Wang, Dacheng Jiang, Xiaojian Liu, Tingting Zhou, Shuang Li, Yuda Wei, Yan Liu, Cheng Hu, Ben Zhou, Jun Qin, Hao Ying, Qiurong Ding

1CAS 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
2School of Pharmacy, East China University of Science and Technology, Shanghai, 200237 P. R. China
3Department of Clinical Laboratory, Linyi People’s Hospital, Xuzhou Medical University, Xuzhou, Shandong 276000 P. R. China
4Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233 China
5CAS 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
6Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101 Beijing, P. R. China