The roles of NFE2L1 in adipocytes: Structural and mechanistic insight from cell and mouse models

• Type of Material: Article
• Authors: Suping Ren, China Medical University; Yiying Bian, China Medical University; Yongyong Hou, China Medical University; Zhendi Wang, China Medical University; Zhuo Zuo, China Medical University; Zhiyuan Liu, China Medical University; Yue Teng, Harbin Medical University; Jingqi Fu, China Medical University; Huihui Wang, China Medical University; Yuanyuan Xu, China Medical University; Qiang Zhang, Emory University; Yanyan Chen, China Medical University; Jingbo Pi, China Medical University
• Language: English
• Date: 2021-08-01
• Publisher: Elsevier Inc
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.redox.2021.102015
• Title of Journal or Parent Work: Redox Biology
• Volume: 44
• Start Page: 102015
• End Page: 102015
• Grant/Funding Information: This research was supported in part by the National Natural Science Foundation of China: 81830099 (J.P.), 82020108027 (J.P.), 81400839 (Y.C.), 82022063 (Y.X.), 81402661 (Y.H.), 81573106 (J.P.), 82073513 (H.W.), 82003500 (Y.B.) and 81402635 (J.F.); National Key R&D Program of China : 2018YFC1311600 (J.P.); and Liaoning Key Research and Development Guidance Plan 2019JH8/10300012 (J.P.). China Postdoctoral Management Foundation YJ20190263 (Y.B).
• Keywords: Adipose; Energy metabolism; Science & Technology; FACTOR-I NRF1; TRANSCRIPTION FACTOR NRF1; INDUCED ANTIOXIDANT RESPONSE; N-TERMINAL DOMAIN; Adipocytes; LONG ISOFORMS; Life Sciences & Biomedicine; FACTOR E2-RELATED FACTOR-1; TNF-ALPHA PROMOTER; Adipogenesis; BROWN ADIPOSE-TISSUE; GENE-EXPRESSION; ENDOPLASMIC-RETICULUM; Biochemistry & Molecular Biology
• Research Categories: Health Sciences, Toxicology

Abstract

Adipocytes play pivotal roles in maintaining energy homeostasis by storing lipids in adipose tissue (AT), regulating the flux of lipids between AT and the circulation in response to the body's energy requirements and secreting a variety of hormones, cytokines and other factors. Proper AT development and function ensure overall metabolic health. Nuclear factor erythroid 2-related factor 1 (NFE2L1, also known as NRF1) belongs to the CNC-bZIP family and plays critical roles in regulating a wide range of essential cellular functions and varies stress responses in many cells and tissues. Human and rodent Nfe2l1 genes can be transcribed into multiple splice variants resulting in various protein isoforms, which may be further modified by a variety of post-translational mechanisms. While the long isoforms of NFE2L1 have been established as master regulators of cellular adaptive antioxidant response and proteasome homeostasis, the exact tissue distribution and physiological function of NFE2L1 isoforms, the short isoforms in particular, are still under intense investigation. With regard to key roles of NFE2L1 in adipocytes, emerging data indicates that deficiency of Nfe2l1 results in aberrant adipogenesis and impaired AT functioning. Intriguingly, a single nucleotide polymorphism (SNP) of the human NFE2L1 gene is associated with obesity. In this review, we summarize the most significant findings regarding the specific roles of the multiple isoforms of NFE2L1 in AT formation and function. We highlight that NFE2L1 plays a fundamental regulatory role in the expression of multiple genes that are crucial to AT metabolism and function and thus could be an important target to improve disease states involving aberrant adipose plasticity and lipid homeostasis.