Limonin's Anti-Dyslipidemic Effects: Investigating the Role of the ILC3-IL-22-IL-22R Pathway in High-Fat Diet-Induced Dyslipidemia

Dyslipidemia significantly increases the risk of ischemic heart disease (IHD). The Western high-fat diet (HFD), a major contributor to dyslipidemia, is often associated with disruptions in gut microbiota and compromised intestinal barrier function. ILC3s, a recently discovered population of innate lymphoid cells primarily found in the gut, respond to dietary and microbial signals by producing IL-22. This cytokine binds to IL-22R expressed on intestinal epithelial cells, thereby maintaining the integrity of the intestinal barrier. Consequently, targeting the ILC3-IL-22-IL-22R pathway to enhance intestinal barrier function holds promise as a therapeutic approach for dyslipidemia. Limonin, obtained from the Chinese herb Euodiae fructus, has shown potential in ameliorating dysbiosis of serum lipids; however, the underlying mechanisms remain unclear. Therefore, this study aimed to investigate the molecular mechanisms underlying the anti-dyslipidemic effects of limonin, focusing on the ILC3-IL-22-IL-22R pathway in mice fed a high-fat diet (HFD).