Abstract

JAZF zinc finger 1 (JAZF1) is involved in glucose and lipid metabolisms. However, its role in aging- and nutrient-related hepatic steatosis is unclear. In the current study, we demonstrated that JAZF1 expression was markedly down-regulated in obesity-associated mice and nonalcoholic fatty liver disease (NAFLD) patients. During aging, JAZF1 expression was gradually down-regulated in both C57BL/6 J and JAZF1-Tg mice. In JAZF1-Tg mice, body fat content and hepatosteatosis were protected from HFD-induced steatosis, and accompanied by decreased lipogenesis gene expression. The inhibitory effects of hepatic steatosis in JAZF1-Tg mice, however, were disappeared during aging. In hepatocytes, over-expression of JAZF1 attenuated, while knockdown of JAZF1 enhanced the expression of lipogenesis genes. The over-expressing of JAZF1 in hepatocytes displayed the increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased sterol regulatory element-binding protein 1c (SREBP-1c) expression. The roles of JAZF1 were partially attenuated by Compound C. Mechanistically, JAZF1 suppressed SREBP-1c expression through the inhibition of transcriptional activity of liver X receptor response elements (LXREs) in the SREBP-1c promoter. Data illustrate that JAZF1 may have a crucial role in the regulation of age and nutrient-associated hepatosteatosis through an AMPK/SREBP-1c-dependent mechanism.

Details

Title
JAZF1 ameliorates age and diet-associated hepatic steatosis through SREBP-1c -dependent mechanism
Author
Qin, Wei 1 ; Zhou, Baoyong 2 ; Yang, Gangyi 3   VIAFID ORCID Logo  ; Hu, Wenjing 3 ; Zhang, Lili 3 ; Liu, Rui 3 ; Li, Minyan 1 ; Wang, Kuan 1 ; Gu, Harvest F 4   VIAFID ORCID Logo  ; Guan, Youfei 5 ; Zhu, Zhiming 6 ; Zheng, Hongting 7   VIAFID ORCID Logo  ; Peng, Jun 5 ; Li, Ling 1   VIAFID ORCID Logo 

1  Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, P. R. China 
2  Department of Hepatobiliary Surgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China 
3  Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China 
4  School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, P. R. China; Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Karolinska Institutet, Huddinge, Stockholm, Sweden 
5  Advanced Institute for Medical Sciences, Dalian Medical University, Liaoning, P. R. China 
6  Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing, P. R. China 
7  Department of Endocrinology, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China 
Pages
1-13
Publication year
2018
Publication date
Aug 2018
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-018-0923-0
ProQuest document ID
2094564100
Copyright
© 2018. 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.