Feng Chang, Li Dandan, Jiang Liping, Liu Xiaofang, Li Qiujuan, Geng Chengyan, Sun Xiance, Yang Guang, Yao Xiaofeng, Chen Min
Department of Preventive Medicine, Dalian Medical University, Dalian, China.
Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, Dalian, China.
Chem Biol Interact. 2017 Aug 1;273:212-218. doi: 10.1016/j.cbi.2017.06.021. Epub 2017 Jun 21.
Citreoviridin (CIT) is a mycotoxin produced by Penicillum citreonigrum, Aspergillus terreus and Eupenicillium ochrosalmoneum. CIT occurs naturally in moldy rice and corn. CIT is associated with the development of atherosclerosis in the general population. Alteration in hepatic lipid metabolism is a pathogenic factor in atherosclerosis. However the effect and the underlying mechanism of CIT on hepatic lipid metabolism are largely unknown. In this study, we reported that CIT induced triglyceride accumulation in mice liver and human liver HepG2 cells as shown in oil red O staining. CIT (0.1 mg/kg-0.3 mg/kg) for 6 weeks elevated liver triglyceride contents in mice. CIT inhibited the transactivation activity of peroxisome proliferator-activated receptor-α (PPAR-α) in hepatocyte in vivo and in vitro, as shown by the reduced mRNA levels of PPAR-α target genes which play key roles in lipid metabolism in various aspects. PPAR-α agonist fenofibrate attenuated CIT-induced triglyceride accumulation in HepG2 cells. Furthermore, CIT increased serum total cholesterol/high-density lipoprotein cholesterol ratio, a strong risk factor for cardiovascular disease. In summary, we reported that CIT induced PPAR-α-dependent hepatic triglyceride accumulation and dyslipidemia. Our data will provide new mechanistic insights into CIT-induced lipid alterations.
黄绿青霉素（CIT）是由黑曲霉、土曲霉和黄棕青霉产生的一种霉菌毒素。CIT天然存在于发霉的大米和玉米中。在普通人群中，CIT与动脉粥样硬化的发展有关。肝脏脂质代谢改变是动脉粥样硬化的致病因素。然而，CIT对肝脏脂质代谢的影响及其潜在机制在很大程度上尚不清楚。在本研究中，我们报告，如油红O染色所示，CIT可诱导小鼠肝脏和人肝癌HepG2细胞中甘油三酯积累。给予小鼠CIT（0.1mg/kg - 0.3mg/kg）6周可提高肝脏甘油三酯含量。如在脂质代谢各方面起关键作用的PPAR-α靶基因的mRNA水平降低所示，CIT在体内和体外均可抑制肝细胞中过氧化物酶体增殖物激活受体-α（PPAR-α）的反式激活活性。PPAR-α激动剂非诺贝特可减轻CIT诱导的HepG2细胞中甘油三酯积累。此外，CIT可提高血清总胆固醇/高密度脂蛋白胆固醇比值，这是心血管疾病的一个重要危险因素。总之，我们报告CIT可诱导PPAR-α依赖性肝脏甘油三酯积累和血脂异常。我们的数据将为CIT诱导的脂质改变提供新的机制见解。
