Quinoa Improves Non‐Alcoholic Fatty Liver Disease by Regulating the Ras‐ <scp>PLD</scp> Pathway to Activate Autophagy

The beneficial effects of quinoa on metabolic diseases have been extensively investigated. In this context, we sought to study the efficacy of quinoa in a nonalcoholic fatty liver disease (NAFLD) mouse model and its underlying mechanism of action. Male ICR mice were fed a high-fat diet for 12 weeks to establish a NAFLD model, followed by 6 weeks of quinoa intervention. The mechanism by which quinoa improves NAFLD was explored using network pharmacology analysis and transcriptome sequencing analysis. Finally, combined with in vivo experiments for verification. Quinoa significantly improved liver damage, abnormal glucose and lipid metabolism, and insulin resistance in NAFLD mice. The results of network pharmacology and transcriptomics indicate that the Ras-PLD signaling pathway and autophagy are key pathways. Quinoa significantly regulates the expression of Ras, Raf, Mek, Erk, and autophagy-related proteins in liver tissue. Meanwhile, quinoa regulates the expression of HNF4A, ACOX2, and glucagon in the liver and pancreas. Our results suggest that quinoa may improve NAFLD by inhibiting the Ras-PLD signaling pathway and activating autophagy, regulating glucose and lipid metabolism and insulin resistance.