Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Inflamm Res. 2023 Sep;72(9):1773-1787. doi: 10.1007/s00011-023-01776-2. Epub 2023 Sep 2.
Previous studies reported that pirfenidone (PFD) is associated with liver disease. However, the effects of pirfenidone on energy metabolism and hepatic lipid accumulation are still poorly understood.
In this study, C57BL/6J mice were randomly divided into two groups, and fed a normal chow diet (NCD) or a high-fat diet (HFD) for 16 weeks. At the end of the eighth week, half of the mice fed on both diets were treated with PFD. Biochemical and lipid metabolism-related indices were analyzed. Furthermore, Hepa 1-6 cells and mouse primary hepatocytes (MPHs) were incubated with PFD with or without free fatty acid (FFA) treatment. Then, stattic (a p-STAT3 inhibitor) or Ad-shSTAT3 was used to further elucidate the effects of Signal Transducer and Activator of Transcription 3 (STAT3) signaling on PFD regulation of hepatic steatosis.
PFD ameliorated obesity and hepatic lipid deposition in HFD mice by decreasing stearoyl-CoA desaturase 1 (SCD1) expression and upregulating p-STAT3 in the liver. In Hepa 1-6 cells and MPHs, PFD also down-regulated the expression of SCD1. STAT3 inhibition treatment eliminated the benefits of PFD on both SCD1 and hepatic steatosis.
In summary, our data reveal that PFD may play an important role in mitigating hepatic steatosis in a STAT3-SCD1-dependent manner.
先前的研究表明，吡非尼酮（PFD）与肝脏疾病有关。然而，吡非尼酮对能量代谢和肝脂质积累的影响仍知之甚少。
在这项研究中，C57BL/6J 小鼠被随机分为两组，分别喂食正常饲料（NCD）或高脂肪饲料（HFD）16 周。在第八周结束时，一半喂食两种饮食的小鼠用 PFD 治疗。分析生化和脂质代谢相关指标。此外，用 PFD 或游离脂肪酸（FFA）处理 Hepa 1-6 细胞和小鼠原代肝细胞（MPHs）。然后，用 stattic（一种 p-STAT3 抑制剂）或 Ad-shSTAT3 进一步阐明信号转导和转录激活因子 3（STAT3）信号对 PFD 调节肝脂肪变性的影响。
PFD 通过降低硬脂酰辅酶 A 去饱和酶 1（SCD1）的表达和上调肝脏中的 p-STAT3，改善了 HFD 小鼠的肥胖和肝脂质沉积。在 Hepa 1-6 细胞和 MPHs 中，PFD 也下调了 SCD1 的表达。STAT3 抑制处理消除了 PFD 对 SCD1 和肝脂肪变性的益处。
综上所述，我们的数据表明，PFD 可能通过 STAT3-SCD1 依赖性途径在减轻肝脂肪变性方面发挥重要作用。
