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• W4310762933 abstract "Abstract Alcoholic liver disease (ALD) is a liver disease caused by long-term heavy alcohol consumption, the initial stage of which is hepatic steatosis. Recent studies have highlighted a possible role for apoptosis-stimulating protein 2 of p53 (ASPP2) in regulating hepatic lipid metabolism. However, the role of ASPP2 in the disease progression of ALD remains unclear. This study aimed to investigate the molecular mechanism of ASPP2 in regulating lipid metabolism in ALD. In the present study, we found that both ASPP2 and peroxisome proliferator-activated receptor (PPARγ) expression were increased in patients with ALD and ethanol-fed mice. To further determine the role of ASPP2 in the development of ALD, we used hepatocyte-specific ASPP2 knockout mice (ASPP2-LKO) to establish an alcoholic liver injury model. We found that deletion of hepatic ASPP2 significantly alleviated hepatic steatosis and injury in a mouse model of ALD. The expression levels of fatty acid oxidation-related genes (AOX, CPT1) and very low-density lipoprotein secretion-related genes (ApoB, MTTP, LFABP) were increased; the expression levels of fatty acid synthesis-related genes (ACC1, FAS) and fatty acid transporter-related genes (CD36) were decreased in ASPP2-LKO mice. Furthermore, we demonstrated that ASPP2 promotes the accumulation of alcohol-induced hepatocyte lipids via HL-7702 cell lines transfected with ASPP2 adenovirus (adv-ASPP2) and ASPP2 short hairpin RNA lentivirus (LV-ASPP2shRNA) under ethanol treatment. Additionally, we found that ASPP2 promoted the expression of PPARγ in vivo and in vitro. Mechanistically, the PPARγ agonist rosiglitazone reversed the protective effect of ASPP2 downregulation on lipid accumulation and liver injury, while the opposite was observed for PPARγ inhibitor T0070907. Collective, ASPP2 exacerbates ethanol-induced hepatic injury and lipid accumulation by upregulating the PPARγ signaling pathway, thus promoting the progression of ALD." @default.
• W4310762933 created "2022-12-17" @default.
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• W4310762933 date "2022-12-06" @default.
• W4310762933 modified "2023-10-17" @default.
• W4310762933 title "ASPP2 deficiency attenuates lipid accumulation through the PPARγ pathway in alcoholic liver injury" @default.
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• W4310762933 doi "https://doi.org/10.21203/rs.3.rs-2311513/v1" @default.
• W4310762933 hasPublicationYear "2022" @default.
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