Speaker
Description
Abstract
Background and Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) has progressed as the most prevalent chronic liver disease globally, affecting over one-third of the world’s population. The perilipin (Plin) family proteins play a crucial role of hepatic lipid droplets (LDs) accumulation in MASLD. This study demonstrates that Paeonol serves as a potential therapeutic agent through regulating the expression of Plin4 during MASLD.
Methods and Results:
Histopathological and biochemical analysis revealed that Paeonol could significantly improve the high-fat diet (HFD)-induced obesity, systemic insulin resistance, dyslipidemia and hepatic steatosis in mice. Untargeted proteomics and transcriptomics were employed to analyze the potential targets of Paeonol treatment indicating that lipid metabolism was the most notably enriched pathway, with Plin4 identified as a common differentially expressed gene (DEGs) and protein (DEPs). Immunohistochemical and Immunofluorescence staining, qPCR and WB suggested that the hepatocyte-specific deficiency of Plin4 protected mice/hepatocytes from hepatic steatosis while overexpression of hepatic Plin4 exacerbated MASLD symptoms and counteracted the ameliorative effects of Paeonol.
Conclusions:
These findings indicates that Plin4 serves as critical regulator in preserving the hepatic fatty acid metabolism homeostasis. Paeonol may emerge as a potential candidate natural component for MASLD.
Keywords: MASLD, Lipid metabolism, Multi-omics, Lipid Droplet-Associated Protein
