脂肪变性
脂肪肝
自噬
化学
脂肪性肝炎
苯并(a)芘
基因剔除小鼠
致癌物
生物化学
脂质代谢
生物
内分泌学
内科学
医学
疾病
基因
细胞凋亡
作者
Yun-Qing Li,Ningjing Liang,Tingting Tang,Zhenzhen Zheng,Muting Chen,Jiao Mo,Ning Zhang,Simi Liao,Lei Yu,Yijie Wu,Chunhua Lan,Huan Ding,Bingxin Du,Mei Feng,Li Wang,Xiaoying Li,Yue Huang,Cailing Lu,Shen Tang,Xiyi Li
标识
DOI:10.1016/j.fct.2023.113986
摘要
Non-alcoholic fatty liver disease (NAFLD) is a progressive disorder of liver metabolism and has become the most common chronic liver disease worldwide. Benzo[a]pyrene (BaP) is recognized as a potent carcinogen, but the effect of low-dose BaP on the development of NAFLD has not been well-studied, and its molecular mechanism is still unknown. In this study, we demonstrated that low-dose BaP induced hepatic steatosis in a mouse model with a notable increase in hepatic lipid content. Interestingly, mRNA expression of genes related to fatty acids uptake or synthesis was not significantly altered after BaP exposure. Instead, we found that low-dose BaP promoted lipid deposition in primary mouse hepatocytes by inhibiting autophagy, which was regulated through Leucine carboxyl methyltransferase-1 (LCMT1) mediated Protein Phosphatases 2A subunit C (PP2Ac) methylation. The role of LCMT1 in BaP-induced steatosis was further validated in a liver-specific lcmt1 knockout (L-LCMT1 KO) mouse model. In this study, we provided evidence to support a novel mechanism by which BaP induces the development of hepatic steatosis through PP2Ac mediated autophagy inhibition. These findings provided new insight into the pathogenesis of NAFLD induced by environmental exposure to low-dose BaP.
科研通智能强力驱动
Strongly Powered by AbleSci AI