Multiscale 3D genome organization underlies duck fatty liver with no adipose inflammation or serious injury

Mengfei Ning, Linfei Song, Xinyu Niu, Yiming Wang, Wenjie Liu, Jiaxiang Hu, Han Cai, Weitao Song, Long Liu, Huifang Li, Daoqing Gong, Jacqueline Smith, Yinhua Huang

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. Little is known about how gene expression and chromatin structure are regulated in NAFLD due to lack of suitable model. Ducks naturally develop fatty liver similar to serious human non-alcoholic fatty liver (NAFL) without adipose inflammation and liver fibrosis, thus serves as a good model for investigating molecular mechanisms of adipose metabolism and anti-inflammation. Here, we constructed a NAFLD model without adipose inflammation and liver fibrosis in ducks. By performing dynamic pathological and transcriptomic analyses, we identified critical genes involving in regulation of the NF-κB and MHCII signaling, which usually lead to adipose inflammation and liver fibrosis. We further generated dynamic three-dimensional chromatin maps during liver fatty formation and recovery. This showed that ducks enlarged hepatocyte cell nuclei to reduce inter-chromosomal interaction, decompress chromatin structure, and alter strength of intra-TAD and loop interactions during fatty liver formation. These changes partially contributed to the tight control the NF-κB and the MHCII signaling. Our analysis uncovers duck chromatin reorganization might be advantageous to maintain liver regenerative capacity and reduce adipose inflammation. These findings shed light on new strategies for NAFLD control.

Original languageEnglish
Article number132452
Pages (from-to)1-14
Number of pages14
JournalInternational Journal of Biological Macromolecules
Volume271
Issue numberPt 1
Early online date20 May 2024
DOIs
Publication statusPublished - Jun 2024

Keywords / Materials (for Non-textual outputs)

  • Chromatin organization
  • Adipose inflammation
  • Duck fatty liver

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