NF-E2-related factor 2 deletion facilitates hepatic fatty acids metabolism disorder induced by high-fat diet via regulating related genes in mice.
There is increasing evidence that Nrf2 participates in hepatic fatty acid metabolism in non-alcoholic fatty liver disease; however, the mechanism remains unclear. We investigated the role of Nrf2 in hepatic fatty acid metabolism disorder induced by high-fat diet (HFD). Mice fed HFD developed hepatic steatosis and exhibited Nrf2 deficiency. Change of fatty acid composition mediated by Nrf2 deletion was observed predominantly in the liver and not the serum. HFD-induced variations in hepatic 18-carbon and 22-carbon fatty acids were enhanced by Nrf2 deficiency. In the HFD group, Nrf2 deficiency led to increases in the mRNA expression of PPARα, FXR, FAS, LXR and ACC-1, while levels of PGC-1α and Srebp-1c mRNA were decreased. Nrf2 mRNA expression was enhanced in the liver of HFD-induced wild type mice, whereas it was undetectable in Nrf2-null mice. These results suggest that Nrf2 deficiency induced by HFD promoted hepatic fatty acid metabolism disorder by altering 18-carbon and 22-carbon fatty acid composition. Changes in fatty acid content were also associated with alteration of the transcription of genes involved in hepatic fatty acid metabolism.
Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address: wangxinghe1987@163.com.
Xinghe
X
Wang
Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address: ar1228@sina.com.
Chunyan
C
Li
Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address: xu_shang_2010@qq.com.
Shang
S
Xu
Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address: ishfaqmuhammad03@gmail.com.
Muhammad
M
Ishfaq
Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address: zhangxiuying@neau.edu.cn.
Xiuying
X
Zhang
D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat; D005227:Fatty Acids / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000235:genetics*
D005227:Fatty Acids; D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse
Fatty acids metabolism; High-fat diet; ICR mice; NAFLD; Nrf2