Forced Hepatic Expression of NRF2 or NQO1 Impedes Hepatocyte Lipid Accumulation in a Lipodystrophy Mouse Model.
Forced Hepatic Expression of NRF2 or NQO1 Impedes Hepatocyte Lipid Accumulation in a Lipodystrophy Mouse Model.
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NRF2或NQO1的强迫肝表达阻碍了脂肪营养不良小鼠模型中的肝脂质积累。
DOI：
10.3390/ijms241713345
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发表时间：
2023-08-28
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
脂肪营养不良是一种疾病，其特征是由于正常脂肪细胞的产生受损而导致正常脂肪组织贮库的损失。它导致异位组织如肝脏和骨骼肌中脂肪沉积的增加，从而导致脂肪变性、血脂异常和胰岛素抵抗。之前，我们建立了Rosa NIC/NIC：：AdiCre脂肪营养不良模型小鼠。脂肪营养不良的表型，包括肝肿大伴随着肝损伤，由于较高的脂质积累，大大减弱了扩增的系统NRF 2信号转导与Keap 1的亚型表达的小鼠;全身NRF 2删除废除这种保护。为了确定肝特异性NRF 2信号传导是否足以保护免于肝肿大和脂肪肝发展，通过在喂食9%脂肪饮食的Rosa NIC/NIC：：AdiCre小鼠中通过流体动力学尾静脉注射显性活性Nrf 2和Nqo 1的pCAG表达载体来实现Nrf 2或其靶基因Nqo 1的直接、强大、瞬时表达。两种载体都能够保护肝脏免受损伤，其中pCAG-Nqo 1载体更有效，如肝脏甘油三酯水平降低约50%所示。因此，激活NRF 2信号或直接升高肝脏中的NQO 1为部分减少伴随脂肪代谢障碍的脂肪变性提供了新的可能性。
Lipodystrophy is a disorder featuring loss of normal adipose tissue depots due to impaired production of normal adipocytes. It leads to a gain of fat deposition in ectopic tissues such as liver and skeletal muscle that results in steatosis, dyslipidemia, and insulin resistance. Previously, we established a Rosa NIC/NIC::AdiCre lipodystrophy model mouse. The lipodystrophic phenotype that included hepatomegaly accompanied with hepatic damage due to higher lipid accumulation was attenuated substantially by amplified systemic NRF2 signaling in mice with hypomorphic expression of Keap1; whole-body Nrf2 deletion abrogated this protection. To determine whether hepatic-specific NRF2 signaling would be sufficient for protection against hepatomegaly and fatty liver development, direct, powerful, transient expression of Nrf2 or its target gene Nqo1 was achieved by administration through hydrodynamic tail vein injection of pCAG expression vectors of dominant-active Nrf2 and Nqo1 in Rosa NIC/NIC::AdiCre mice fed a 9% fat diet. Both vectors enabled protection from hepatic damage, with the pCAG-Nqo1 vector being the more effective as seen with a ~50% decrease in hepatic triglyceride levels. Therefore, activating NRF2 signaling or direct elevation of NQO1 in the liver provides new possibilities to partially reduce steatosis that accompanies lipodystrophy.
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影响因子：
29
作者：
Cortés VA;Curtis DE;Sukumaran S;Shao X;Parameswara V;Rashid S;Smith AR;Ren J;Esser V;Hammer RE;Agarwal AK;Horton JD;Garg A
通讯作者：
Garg A
影响因子：
7.7
作者：
Hwang JH;Kim DW;Jo EJ;Kim YK;Jo YS;Park JH;Yoo SK;Park MK;Kwak TH;Kho YL;Han J;Choi HS;Lee SH;Kim JM;Lee I;Kyung T;Jang C;Chung J;Kweon GR;Shong M
通讯作者：
Shong M
DOI：
10.3390/antiox12030595
发表时间：
2023-02-27
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
通讯作者：
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DOI：
10.1164/rccm.201102-0271oc
发表时间：
2011-10-15
影响因子：
24.7
作者：
Kong, Xiaoni;Thimmulappa, Rajesh;Biswal, Shyam
通讯作者：
Biswal, Shyam
影响因子：
10.5
作者：
Itoh, K;Wakabayashi, N;Yamamoto, M
通讯作者：
Yamamoto, M