Found programs: Natural Science Foundation of Inner Mongolia Autonomous Region (No.2023MS08026);Health Science and Technology Project of Inner Mongolia Autonomous Region (No.202201430);Youth Innovative Talent Project of Baotou (No.YFYRC-QCRC-2023001);Graduate Student Research Innovation Project of Baotou Medical College (No.bycx2023022)
Authors:Wang Haiyan; Zhang Yuxin; Zhu Li; Ma Ruiting; Zhang Yonghong
Keywords:nonalcoholic fatty liver disease;bisphenol A;miR-122-5p;miR-143-3p;inflammatory factors
DOI:DOI:10.19405/j.cnki.issn1000-1492.2024.10.011
〔Abstract〕 Objective To explore the impact of bisphenol A(BPA) exposure on liver lipid metabolism in C57BL/6J mice and uncover the mechanisms at work. Methods Male C57BL/6J mice, aged eight weeks, were stratified into six cohorts: a control group on a standard diet(ND), a group on a standard diet with low-dose BPA(BPA-50 ND), a group on a standard diet with high-dose BPA(BPA-500 ND), a control groupon a high-fat diet(HFD), a group on a high-fat diet with low-dose BPA(BPA-50 HFD), and a group on a high-fat diet with high-dose BPA(BPA-500 HFD). Dosages for the low-and high-dose BPA groups were 50 and 500 μg/(kg·d), respectively, administeredviagavage over a duration of 12 weeks. Hepatic tissue underwent histological examination through hematoxylin and eosin(HE) staining. Furthermore, the expression levels of miR-122-5p and miR-143-3p in hepatic tissue, in addition to interleukin(IL)-6 and IL-10 in peripheral serum, were quantitatively measured employing quantitative reverse transcription-polymerase chain reaction(qRT-PCR) and enzyme-linked immunosorbent assay(ELISA), respectively. Results Histopathological analysisviaHE staining indicated intact hepatic lobule architecture in the ND group, whereas other groups displayed variable degrees of lipid droplet accumulation and damage to hepatic lobules. Notably, supplementation with BPA, particularly in conjunction with a high-fat diet, led to a progressive increase in IL-6 levels and a decrease in IL-10 levels in peripheral blood. In the context of a standarddiet, an augmentation in BPA concentration corresponded with a decline in the expression of miR-122-5p and miR-143-3p. Conversely, within the high-fat diet cohort, enhanced BPA concentrations were associated with increased expressions of these microRNAs. Pearson correlation analysis disclosed a significant positive correlation between the expression of miR-122-5p and miR-143-3p and the level of IL-10 in the standard diet group(P<0.01). In the high fat diet group, the expression level of miR-122-5p was positively correlated with the concentration of IL-6(P<0.05), and the expression level of miR-143-3p was negatively correlated with the concentration of IL-10(P<0.05). Conclusion BPA can induce the occurrence and progression of nonalcoholic fatty liver disease(NAFLD) by regulating the expression of miR-122-5p and miR-143-3p and regulating the levels of inflammatory factors IL-6 and IL-10.