Copper induces liver lipotoxicity disease by up-regulating Nrf2 expression via the activation of MTF-1 and inhibition of SP1/Fyn pathway

Chong-Chao Zhong; Tao Zhao; Christer Hogstrand; Chang-Chun Song; Ester Zito; Xiao-Ying Tan; Yu Feng Song; Xiao-Lei Wei; Zhi Luo

doi:10.1016/j.bbadis.2023.166752

Copper induces liver lipotoxicity disease by up-regulating Nrf2 expression via the activation of MTF-1 and inhibition of SP1/Fyn pathway

Chong-Chao Zhong, Tao Zhao, Christer Hogstrand, Chang-Chun Song, Ester Zito, Xiao-Ying Tan, Yu Feng Song, Xiao-Lei Wei, Zhi Luo^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Excessive copper (Cu) intake leads to hepatic lipotoxicity disease, which has adverse effects on health, but the underlying mechanism is unclear. We found that Cu increased lipotoxicity by promoting Nrf2 recruitment to the ARE site in the promoters of five lipogenic genes (g6pd, 6pgd, me, icdh and pparγ). We also found that Cu affected the Nrf2 expression via different pathways: metal regulatory transcription factor 1 (MTF-1) mediated the Cuinduced Nrf2 transcriptional activation; Cu also enhanced the expression of Nrf2 by inhibiting the SP1 expression, which was achieved by inhibiting the negative regulator Fyn of Nrf2. These promoted the enrichment of Nrf2 in the nucleus and ultimately affected lipotoxicity. Thus, for the first time, we elucidated that Cu induced liver lipotoxicity disease by up-regulating Nrf2 expression via the MTF-1 activation and the inhibition of SP1/Fyn pathway. Our study elucidates the Cu-associated obesity and NAFLD for fish and possibly humans.

Original language	English
Article number	166752
Journal	BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume	1869
Issue number	6
DOIs	https://doi.org/10.1016/j.bbadis.2023.166752
Publication status	Published - 22 May 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bbadis.2023.166752Licence: CC BY

Cite this

Zhong, C.-C., Zhao, T., Hogstrand, C., Song, C.-C., Zito, E., Tan, X.-Y., Song, Y. F., Wei, X.-L., & Luo, Z. (2023). Copper induces liver lipotoxicity disease by up-regulating Nrf2 expression via the activation of MTF-1 and inhibition of SP1/Fyn pathway. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1869(6), Article 166752. https://doi.org/10.1016/j.bbadis.2023.166752

@article{beb9b862cc0e406186f065a897978d81,

title = "Copper induces liver lipotoxicity disease by up-regulating Nrf2 expression via the activation of MTF-1 and inhibition of SP1/Fyn pathway",

abstract = "Excessive copper (Cu) intake leads to hepatic lipotoxicity disease, which has adverse effects on health, but the underlying mechanism is unclear. We found that Cu increased lipotoxicity by promoting Nrf2 recruitment to the ARE site in the promoters of five lipogenic genes (g6pd, 6pgd, me, icdh and pparγ). We also found that Cu affected the Nrf2 expression via different pathways: metal regulatory transcription factor 1 (MTF-1) mediated the Cuinduced Nrf2 transcriptional activation; Cu also enhanced the expression of Nrf2 by inhibiting the SP1 expression, which was achieved by inhibiting the negative regulator Fyn of Nrf2. These promoted the enrichment of Nrf2 in the nucleus and ultimately affected lipotoxicity. Thus, for the first time, we elucidated that Cu induced liver lipotoxicity disease by up-regulating Nrf2 expression via the MTF-1 activation and the inhibition of SP1/Fyn pathway. Our study elucidates the Cu-associated obesity and NAFLD for fish and possibly humans. ",

author = "Chong-Chao Zhong and Tao Zhao and Christer Hogstrand and Chang-Chun Song and Ester Zito and Xiao-Ying Tan and Song, {Yu Feng} and Xiao-Lei Wei and Zhi Luo",

note = "Funding Information: The present study is funded by National Natural Science Foundation of China ( 31872585 ) and National Key Research and Development Program of China ( 2018YFD0900400 ). Publisher Copyright: {\textcopyright} 2023 Elsevier B.V.",

year = "2023",

month = may,

day = "22",

doi = "10.1016/j.bbadis.2023.166752",

language = "English",

volume = "1869",

journal = "BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE",

issn = "0925-4439",

publisher = "Elsevier",

number = "6",

}

TY - JOUR

T1 - Copper induces liver lipotoxicity disease by up-regulating Nrf2 expression via the activation of MTF-1 and inhibition of SP1/Fyn pathway

AU - Zhong, Chong-Chao

AU - Zhao, Tao

AU - Hogstrand, Christer

AU - Song, Chang-Chun

AU - Zito, Ester

AU - Tan, Xiao-Ying

AU - Song, Yu Feng

AU - Wei, Xiao-Lei

AU - Luo, Zhi

N1 - Funding Information: The present study is funded by National Natural Science Foundation of China ( 31872585 ) and National Key Research and Development Program of China ( 2018YFD0900400 ). Publisher Copyright: © 2023 Elsevier B.V.

PY - 2023/5/22

Y1 - 2023/5/22

N2 - Excessive copper (Cu) intake leads to hepatic lipotoxicity disease, which has adverse effects on health, but the underlying mechanism is unclear. We found that Cu increased lipotoxicity by promoting Nrf2 recruitment to the ARE site in the promoters of five lipogenic genes (g6pd, 6pgd, me, icdh and pparγ). We also found that Cu affected the Nrf2 expression via different pathways: metal regulatory transcription factor 1 (MTF-1) mediated the Cuinduced Nrf2 transcriptional activation; Cu also enhanced the expression of Nrf2 by inhibiting the SP1 expression, which was achieved by inhibiting the negative regulator Fyn of Nrf2. These promoted the enrichment of Nrf2 in the nucleus and ultimately affected lipotoxicity. Thus, for the first time, we elucidated that Cu induced liver lipotoxicity disease by up-regulating Nrf2 expression via the MTF-1 activation and the inhibition of SP1/Fyn pathway. Our study elucidates the Cu-associated obesity and NAFLD for fish and possibly humans.

AB - Excessive copper (Cu) intake leads to hepatic lipotoxicity disease, which has adverse effects on health, but the underlying mechanism is unclear. We found that Cu increased lipotoxicity by promoting Nrf2 recruitment to the ARE site in the promoters of five lipogenic genes (g6pd, 6pgd, me, icdh and pparγ). We also found that Cu affected the Nrf2 expression via different pathways: metal regulatory transcription factor 1 (MTF-1) mediated the Cuinduced Nrf2 transcriptional activation; Cu also enhanced the expression of Nrf2 by inhibiting the SP1 expression, which was achieved by inhibiting the negative regulator Fyn of Nrf2. These promoted the enrichment of Nrf2 in the nucleus and ultimately affected lipotoxicity. Thus, for the first time, we elucidated that Cu induced liver lipotoxicity disease by up-regulating Nrf2 expression via the MTF-1 activation and the inhibition of SP1/Fyn pathway. Our study elucidates the Cu-associated obesity and NAFLD for fish and possibly humans.

UR - http://www.scopus.com/inward/record.url?scp=85159799175&partnerID=8YFLogxK

U2 - 10.1016/j.bbadis.2023.166752

DO - 10.1016/j.bbadis.2023.166752

M3 - Article

SN - 0925-4439

VL - 1869

JO - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

JF - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

IS - 6

M1 - 166752

ER -

Copper induces liver lipotoxicity disease by up-regulating Nrf2 expression via the activation of MTF-1 and inhibition of SP1/Fyn pathway

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this