The roles of NFE2L1 in adipocytes: Structural and mechanistic insight from cell and mouse models
Suping Ren,
Yiying Bian,
Yongyong Hou,
Zhendi Wang,
Zhuo Zuo,
Zhiyuan Liu,
Yue Teng,
Jingqi Fu,
Huihui Wang,
Yuanyuan Xu,
Qiang Zhang,
Yanyan Chen,
Jingbo Pi
Affiliations
Suping Ren
Program of Environmental Toxicology, School of Public Health, China Medical University. No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China
Yiying Bian
Program of Environmental Toxicology, School of Public Health, China Medical University. No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China
Yongyong Hou
Program of Environmental Toxicology, School of Public Health, China Medical University. No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China
Zhendi Wang
Program of Environmental Toxicology, School of Public Health, China Medical University. No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China
Zhuo Zuo
Program of Environmental Toxicology, School of Public Health, China Medical University. No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China
Zhiyuan Liu
Program of Environmental Toxicology, School of Public Health, China Medical University. No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China
Yue Teng
Department of Hepatopancreatobiliary Surgery, The Forth Affiliated Hospital, Harbin Medical University, Harbin, China
Jingqi Fu
Program of Environmental Toxicology, School of Public Health, China Medical University. No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China
Huihui Wang
Group of Chronic Disease and Environmental Genomics, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China
Yuanyuan Xu
Group of Chronic Disease and Environmental Genomics, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China
Qiang Zhang
Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, GA, 30322, USA
Yanyan Chen
The First Affiliated Hospital, China Medical University, No. 155 Nanjing North Road, Heping Area, Shenyang, Liaoning, 110001, China; Corresponding author. The First Affiliated Hospital, China Medical University, No. 155 Nanjing North Road, Heping Area, Shenyang, Liaoning, 110001, China.
Jingbo Pi
Program of Environmental Toxicology, School of Public Health, China Medical University. No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China; Corresponding author. School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, China.,
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.
