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Inflammation Research

Erschienen in:

02.09.2023 | Original Research Paper

Pirfenidone ameliorates liver steatosis by targeting the STAT3-SCD1 axis

verfasst von: Shan Yang, Renzi Zhang, Wenzhen Deng, Shichuan Chang, Yang Li, Sheng Li

Erschienen in: Inflammation Research | Ausgabe 9/2023

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Abstract

Objective

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.

Methods

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.

Results

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.

Conclusion

In summary, our data reveal that PFD may play an important role in mitigating hepatic steatosis in a STAT3-SCD1-dependent manner.

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Titel: Pirfenidone ameliorates liver steatosis by targeting the STAT3-SCD1 axis
verfasst von: Shan Yang
Renzi Zhang
Wenzhen Deng
Shichuan Chang
Yang Li
Sheng Li
Publikationsdatum: 02.09.2023
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 9/2023
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-023-01776-2

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