Abstract

In obese adults, nonalcoholic fatty liver disease (NAFLD) is accompanied by multiple metabolic dysfunctions. Although upregulated hepatic fatty acid synthesis has been identified as a crucial mediator of NAFLD development, the underlying mechanisms are yet to be elucidated. In this study, we reported upregulated expression of gene related to anergy in lymphocytes (GRAIL) in the livers of humans and mice with hepatic steatosis. Grail ablation markedly alleviated the high-fat diet-induced hepatic fat accumulation and expression of genes related to the lipid metabolism, in vitro and in vivo. Conversely, overexpression of GRAIL exacerbated lipid accumulation and enhanced the expression of lipid metabolic genes in mice and liver cells. Our results demonstrated that Grail regulated the lipid accumulation in hepatic steatosis via interaction with sirtuin 1. Thus, Grail poses as a significant molecular regulator in the development of NAFLD.

Details

Title
E3 ubiquitin ligase Grail promotes hepatic steatosis through Sirt1 inhibition
Author
Pei-Yao, Liu 1 ; Cheng-Cheung, Chen 2 ; Chia-Ying, Chin 3 ; Te-Jung, Liu 4 ; Tsai Wen-Chiuan 5 ; Jian-Liang, Chou 6 ; Chuan-Yu, Huang 6 ; Yu-Guang, Chen 7 ; Chen, Ying-Chuan 8 

 Department of Physiology & Biophysics, National Defense Medical Center, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356) 
 Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356) 
 Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356); Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356) 
 Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, Taipei, Taiwan (GRID:grid.278244.f) (ISNI:0000 0004 0638 9360); Department of Physical Medicine and Rehabilitation, School of Medicine, National Defense Medical Center, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356); Department of Physical Medicine and Rehabilitation, Taoyuan Armed Force General Hospital, Taoyuan, Taiwan (GRID:grid.260565.2) 
 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (GRID:grid.260565.2); Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356) 
 Instrument Center, Department of Research and Development, National Defense Medical Center, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356) 
 Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (GRID:grid.260565.2); University College London, Cancer Institute, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201) 
 Department of Physiology & Biophysics, National Defense Medical Center, Taipei, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356); Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan (GRID:grid.260565.2) (ISNI:0000 0004 0634 0356) 
Publication year
2021
Publication date
Mar 2021
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2505573481
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.