Ling-gui-zhu-gan decoction alleviates hepatic steatosis through SOCS2 modification by N6-methyladenosine - 30/05/20
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Graphical abstract |
Highlights |
• | LGZG decoction alleviated HFD-induced hepatic steatosis. |
• | LGZG decoction reduced m6A methylation levels. |
• | The most crucial modification site of m6A methylation was the CDS domain. |
• | The mechanism may be related to the m6A-medicated SOCS2 expression. |
Abstract |
Background |
The ling-gui-zhu-gan (LGZG) decoction is a classic formula in traditional chinese medicine (TCM) and is widely used in clinical settings. Recently, the LGZG decoction was demonstrated to have an effect in alleviating hepatic steatosis induced by a high-fat diet (HFD). However, the mechanisms underlying this therapeutic effect remain unclear. The present study was designed to evaluate the effect and explore possible mechanisms of action of the LGZG decoction in nonalcoholic fatty liver disease (NAFLD).
Methods |
Liver tissue and blood samples were harvested. Liver steatosis, triglyceride (TG), liver total cholesterol (TC), liver low-density lipoprotein (LDL), serum almandine aminotransferase (ALT), aspartate aminotransferase (AST), and free fatty acid (FFA) were assayed. N6-methyladenosine (m6A) levels were estimated using an m6A RNA methylation quantification kit and immunohistochemistry. The m6A methylome was detected through methylated RNA immunoprecipitation sequencing (MeRIP-seq), followed by data analysis. The expression levels of differentially methylated genes (DMGs) were determined using real-time polymerase chain reaction and western blotting.
Results |
The LGZG decoction significantly alleviated hepatic steatosis and reduced m6A levels. MeRIP-seq revealed the coding sequence (CDS) domain to be the most critical modification site for m6A methylation, and the molecular functions of DMGs predominantly included insulin-like growth factor receptor binding and fatty acid metabolism and degradation. Further, LGZG treatment could reduce the m6A methylation levels of suppressor of cytokine signaling 2 (SOCS2), along with the expression of SOCS2 at mRNA and protein levels.
Conclusions |
The LGZG decoction is an effective formula for treating NAFLD, and the possible mechanisms underlying its action could be related to N6-methyladenosine modification-medicated SOCS2.
Le texte complet de cet article est disponible en PDF.Keywords : Ling-gui-zhu-gan decoction, Nonalcoholic fatty liver disease, N6-methyladenosine modification, SOCS2, Hepatic steatosis
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