Abstract
BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is becoming the most common form of chronic liver disease worldwide. We explored the potential mechanisms responsible for the protective role of sleeve gastrectomy (SG) on MASLD in a high-fat diet (HFD) rat model. MethodsRats were fed with HFD for 12 weeks to generate MASLD model that were subjected to SG or sham surgery. The endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyric acid (4-PBA) was injected intraperitoneally every day for 4 weeks after surgery to identify the impact of ERS. ResultsThe MASLD rat model was generated successfully, as indicated by significant upregulation of metabolic parameters. Fibroblast growth factor 21 (FGF21) and ERS-related proteins were increased in HFD rats, while expression of fibroblast growth factor receptor 1 was decreased as expected. An HFD also induced swelling and blurring of the endoplasmic reticulum and mitochondria in hepatocytes, and the above transformation could be relieved by SG and 4-PBA. SG and an ERS inhibitor both inhibited MASLD, but their combined treatment had no additional benefit. ConclusionsDysfunction of the FGF21 signaling pathway and hepatic steatosis and inflammation could be induced by an HFD, potentially causing MASLD. Bariatric surgery and ERS inhibition could alleviate MASLD by relieving ERS-mediated impairment of FGF21 signal transduction. These findings provide a new insight into the use of ERS inhibitors to treat MASLD, especially in patients who prefer to avoid surgery.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Clinics and Research in Hepatology and Gastroenterology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
