Raspberry ketone improves non-alcoholic fatty liver disease induced in rats by modulating sphingosine kinase/sphingosine-1-phosphate and toll-like receptor 4 pathways.

This article investigates the therapeutic effects of raspberry ketone (RK), a natural aromatic compound, and calorie-restricted (CR) diet on non-alcoholic fatty liver disease (NAFLD) induced in rats by a high-fat fructose diet (HFFD). The study focuses on the modulation of sphingosine kinase-1 (SphK1)/sphingosine-1-phosphate (S1P) and toll-like receptor 4 (TLR4) signaling pathways, which are implicated in NAFLD pathogenesis through their roles in lipid metabolism, inflammation, and oxidative stress. Results showed that both RK supplementation with a normal diet and CR diet significantly improved liver function, reduced hepatic fat accumulation, oxidative stress, and inflammation, and downregulated hepatic SphK1, S1P, S1P receptor 1 (S1PR1), TLR4, and NF-κB levels; notably, RK treatment often yielded superior outcomes compared to CR alone. The findings suggest that RK could serve as a promising therapeutic agent for NAFLD patients unable to adhere to calorie restriction by targeting interconnected metabolic and inflammatory pathways involved in disease progression.