Limonin and Dyslipidemia: Investigating the Role of Gut Barrier and Microbiota

Limonin has been shown to reduce serum total cholesterol (TC) and triglyceride (TG) levels in obese mice (Halder et al., 2014). It also diminishes the accumulation of lipid droplets in the liver and downregulates the levels of lipogenic transcription factors, such as FASN and SREBP1, in non-alcoholic fatty liver disease (NAFLD) (Li et al., 2021). Additionally, limonin has been reported to alleviate indomethacin-induced intestinal damage and ulcers. Furthermore, limonin therapy has been found to enrich the abundance of Bacteroidetes while inhibiting Firmicutes. It also significantly boosts the population of the genus Oscillospira, leading to reduced occurrences of inflammatory bowel disease and leanness in humans (Gu et al., 2019). However, it is unclear whether the improvement of dyslipidemia by limonin is associated with the regulation of the gut barrier and gut microbiota. Therefore, the objective of this study was to investigate whether limonin's effect on dyslipidemia induced by a high-fat diet (HFD) is related to the integrity of the intestinal barrier and the composition of the intestinal microbiota. Additionally, we aimed to explore the underlying mechanism based on the ILC3-IL-22-IL-22R pathway.