Torularhodin Alleviates Hepatic Dyslipidemia and Inflammations in High-Fat Diet-Induced Obese Mice via PPARα Signaling Pathway

Torularhodin is a β-carotene-like compound from Sporidiobolus pararoseus, and its protective effect against high-fat diet (HFD)-induced hepatic dyslipidemia and inflammation was investigated. Compared to mice of C57BL/6J fed on HFD, the addition of Torularhodin into the HFD (HFD-T) significantly reduced body weight, serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and the inflammatory mediators of TNF-α, IL-6, IL-1β, and lipopolysaccharide (LPS). A significant increase of high-density lipoprotein cholesterol (HDL-c), which is beneficial to cholesterol clearance, was also observed in HFD-T group. Proteomic analysis showed HDL-C-c is highly correlated with proteins (e.g., CPT1A and CYP7A1) involved in lipid β-oxidation and bile acid synthesis, whereas the other phenotypic parameters (TC, TG, LDL, and inflammatory cytokines) are highly associated with proteins (e.g., SLC27A4) involved in lipid-uptake. The up-regulated anti-inflammation proteins FAS, BAX, ICAM1, OCLN, GSTP1, FAF1, LRP1, APEX1, ROCK1, MANF, STAT3, and INSR and down-regulated pro-inflammatory proteins OPTN, PTK2B, FADD, MIF, CASP3, YAP1, DNM1L, and NAMPT not only demonstrate the occurrence of HFD-induced hepatic inflammation, but also prove the anti-inflammatory property of Torularhodin. KEGG signaling pathway analysis revealed that the PPARα signaling pathway is likely fundamental to the health function of Torularhodin through up-regulating genes related to fatty acid β-oxidation, cholesterol excretion, HDL-Cc formation, and anti-inflammation. Torularhodin, as a new food resource, may act as a therapeutic agent to prevent hepatic dyslipidemia and related inflammation for improved health.