Royal jelly acid improves hyperlipidemia through the gut-liver axis mediated SCFAs-glycerophospholipid pathway

The incidence of hyperlipidemia, a lipid metabolic disorder, continues to increase globally, but current pharmacological therapies are often limited by adverse effects. Royal jelly acid, a unique monounsaturated fatty acid (MUFA) derived from royal jelly, shows therapeutic promise against hyperlipidemia; however, its direct targets and regulatory mechanisms remain unclear. In a diet-induced rat model of hyperlipidemia, royal jelly acid exhibited favorable safety and significantly improved body weight, serum lipid indices, hepatic enzyme activity, and antioxidant capacity, while alleviating hepatic lipid droplet accumulation. Royal jelly acid significantly increased the abundance of short-chain fatty acid (SCFA)-producing intestinal microorganisms, promoted SCFA production, and restored hyperlipidemia-associated intestinal microbial imbalance. Liver transcriptomic and plasma metabolomic analyses demonstrated that royal jelly acid regulated genes involved in glycolipid metabolism, oxidative stress, and inflammatory responses, as well as multiple key metabolites. Integrated multi-omics analysis and molecular docking confirmed that the glycerophospholipid metabolic pathway represents the core metabolic axis mediating these protective effects. Royal jelly acid mainly alleviates hyperlipidemia by enhancing antioxidant and anti-inflammatory defense through the gut–liver axis–mediated SCFAs–glycerophospholipid pathway. These findings support the use of royal jelly acid as a promising MUFA-based therapeutic strategy for hyperlipidemia and provide a scientific basis for its application.