Neohesperidin Dihydrochalcone Ameliorates High-Fat Diet-Induced Glycolipid Metabolism Disorder in Rats.

High-fat diet (HFD) is closely related to the formation of metabolic diseases. Studies have confirmed that neohesperidin dihydrochalcone (NHDC) possesses the biological activity of preventing glycolipid metabolism disorder. To explore the mechanism of its preventive activity against glucolipid metabolism disorder, HFD-treated rats were orally administered with NHDC for 12 weeks continuously. The results showed that, compared with the HFD group, the intervention of 40-80 mg/kg body weight of NHDC effectively downregulated the level of fasting blood glucose. Western blot analysis revealed that the treatment of NHDC alleviated the inhibitory effect of HFD on the expression of hepatic GLUT-4 and IRS-1. Further studies confirmed that NHDC reduced the degree of HFD-stimulated inflammation of ileum through the TLR4/MyD88/NF-κB signaling pathway. Moreover, ileum intestinal flora analysis showed that intragastric administration of NHDC reversed the change of Proteobacteria abundance and the Firmicutes/Bacteroidetes (F/B) ratio caused by HFD. At the generic level, NHDC promoted the relative abundance of Coprococcus, Bifidobacterium, Clostridium, Oscillospira, and [Eubacterium], while reducing the relative abundance of Defluviitalea and Prevotella. Taken together, these findings suggest that NHDC possesses the biological activity of improving HFD-induced glycolipid metabolism disorder.