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• W2943873997 abstract "Nonalcoholic fatty liver disease (NAFLD) is more sensitive to ischemia and reperfusion injury (IRI), while there are no effective methods to alleviate IRI. Necroptosis, also known as “programmed necrosis,” incorporates features of necrosis and apoptosis. However, the role of necroptosis in IRI of the fatty liver remains largely unexplored. In the present study, we aimed to assess whether necroptosis was activated in the fatty liver and whether such activation accelerated IRI in the fatty liver. In this study, we found that the liver IRI was enhanced in HFD-fed mice with more release of TNF α . TNF α and supernatant of macrophages could induce necroptosis of hepatocytes in vitro . Necroptosis was activated in NAFLD, leading to more severe IRI, and such necroptosis could be inhibited by TN3-19.12, the neutralizing monoclonal antibody against TNF α . Pretreatment with Nec-1 and GSK<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M1><mml:msup><mml:mrow /><mml:mrow><mml:mo>′</mml:mo></mml:mrow></mml:msup></mml:math>872, two inhibitors of necroptosis, significantly reduced the liver IRI and ROS production in HFD-fed mice. Moreover, the inhibition of necroptosis could decrease ROS production of hepatocytes in vitro . Inflammatory response was activated during IRI, and necroptosis inhibitors could suppress signaling pathways of inflammation and the soakage of inflammation cells. In conclusion, TNF α -induced necroptosis played an important role during IRI in the fatty liver. Our findings demonstrated that necroptosis might be a potential target to reduce the fatty liver-associated IRI." @default.
• W2943873997 created "2019-05-16" @default.
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• W2943873997 date "2019-05-12" @default.
• W2943873997 modified "2023-10-16" @default.
• W2943873997 title "TNF<i>α</i>-Mediated Necroptosis Aggravates Ischemia-Reperfusion Injury in the Fatty Liver by Regulating the Inflammatory Response" @default.
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• W2943873997 doi "https://doi.org/10.1155/2019/2301903" @default.
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