Pei-Yao Liu1, Cheng-Cheung Chen2, Chia-Ying Chin2,3, Te-Jung Liu4,5,6, Wen-Chiuan Tsai7,8, Jian-Liang Chou9, Chuan-Yu Huang9, Yu-Guang Chen10,11, Ying-Chuan Chen12,13. 1. Department of Physiology & Biophysics, National Defense Medical Center, Taipei, 114, Taiwan. 2. Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan. 3. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 114, Taiwan. 4. Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, Taipei, 114, Taiwan. 5. Department of Physical Medicine and Rehabilitation, School of Medicine, National Defense Medical Center, Taipei, 114, Taiwan. 6. Department of Physical Medicine and Rehabilitation, Taoyuan Armed Force General Hospital, Taoyuan, 114, Taiwan. 7. Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan. 8. Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei, 114, Taiwan. 9. Instrument Center, Department of Research and Development, National Defense Medical Center, Taipei, 114, Taiwan. 10. Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan. 11. Cancer Institute, University College London, London, UK. 12. Department of Physiology & Biophysics, National Defense Medical Center, Taipei, 114, Taiwan. addy0918@gmail.com. 13. Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan. addy0918@gmail.com.
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.
In obese adults, pan class="Disease">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 andmice 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.
Authors: Jill M Schartner; William T Simonson; Sarah A Wernimont; Lauren M Nettenstrom; Anna Huttenlocher; Christine M Seroogy Journal: J Biol Chem Date: 2009-10-15 Impact factor: 5.157
Authors: Leon A Adams; James F Lymp; Jenny St Sauver; Schuyler O Sanderson; Keith D Lindor; Ariel Feldstein; Paul Angulo Journal: Gastroenterology Date: 2005-07 Impact factor: 22.682
Authors: Syed F Hassnain Waqas; Anh Cuong Hoang; Ya-Tin Lin; Grace Ampem; Hind Azegrouz; Lajos Balogh; Julianna Thuróczy; Jin-Chung Chen; Ivan C Gerling; Sorim Nam; Jong-Seok Lim; Juncal Martinez-Ibañez; José T Real; Stephan Paschke; Raphaëlle Quillet; Safia Ayachi; Frédéric Simonin; E Marion Schneider; Jacqueline A Brinkman; Dudley W Lamming; Christine M Seroogy; Tamás Röszer Journal: J Clin Invest Date: 2017-06-05 Impact factor: 14.808
Authors: Christopher D Williams; Joel Stengel; Michael I Asike; Dawn M Torres; Janet Shaw; Maricela Contreras; Cristy L Landt; Stephen A Harrison Journal: Gastroenterology Date: 2010-09-19 Impact factor: 22.682