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  2. Copper (Cu) induced changes of lipid metabolism through oxidative stress-mediated autophagy and Nrf2/PPARγ pathways

Copper (Cu) induced changes of lipid metabolism through oxidative stress-mediated autophagy and Nrf2/PPARγ pathways

  • J Nutr Biochem. 2022 Feb;100:108883. doi: 10.1016/j.jnutbio.2021.108883.
Chong-Chao Zhong 1 Tao Zhao 1 Christer Hogstrand 2 Fang Chen 1 Chang-Chun Song 1 Zhi Luo 3
Affiliations

Affiliations

  • 1 Laboratory of Molecular Nutrition and Health, Fishery College, Huazhong Agricultural University, Wuhan Hubei Province, China.
  • 2 Diabetes and Nutritional Sciences Division, School of Medicine, King's College London, London, UK.
  • 3 Laboratory of Molecular Nutrition and Health, Fishery College, Huazhong Agricultural University, Wuhan Hubei Province, China; Hubei Hongshan Laboratory, Wuhan, Hubei Province, China. Electronic address: luozhi99@mail.hzau.edu.cn.
Abstract

Oxidative stress can induce occurrence of non-alcoholic fatty liver disease (NAFLD). Nrf2 is a central regulator of cellular oxidative stress and also participates in the control of lipid deposition and metabolism. Here, we hypothesize that oxidative stress-mediated Nrf2 activation participates in the regulation of the Cu-induced lipid deposition. We found that Cu excess activated oxidative stress and Autophagy, up-regulated lipogenesis and lipid metabolism, suppressed Keap1 expression and activated Nrf2 signaling. Moreover, Cu induced lipid deposition via oxidative stress and the mitochondrial dysfunction. Oxidative stress mediated Cu-induced activation of Nrf2 and Autophagy. The activation of Autophagy helps to alleviate Cu-induced lipid deposition and accordingly provided a protective role against Cu-induced NAFLD. Meantime, Cu-induced oxidative stress promoted Nrf2 recruitment to the PPARγ promoter, inducing target gene transcription, and subsequent lipogenesis. Our findings, for the first time, provide direct evidences for Nrf2 function in the modulation of lipogenic metabolism via the transcriptional activation of PPARγ, and elucidate the mechanisms by which Nrf2 functions as the central regulator of lipogenic genes and highlights the significance of Nrf2 as potential therapeutic targets for oxidative stress-associated obesity and NAFLD for fish and human beings.

Keywords

Copper; Lipid metabolism; Molecular mechanisms; Nrf2/PPARγ pathway; Oxidative stress.

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