ABSTRACT: Purpose: Naringin (Nar) is a dihydroflavonoid compound, which is widely found in Chinese herbal medicine and citrus fruit. As one of the phytochemicals, it acts as a dietary supplement and can delay aging and prevent aging-related disease, such as obesity and diabetes. However, the exact mechanism still partially remained unclear. Methods: In this study, the high-glucose induced (HGI) Caenorhabditis elegans model was used to evaluate the anti-aging and anti-obesity effects of Nar. Results: It indicated that the mean lifespan and fast movement span of HGI worms were extended roughly 24% and 11% by Nar treatment, respectively. Oil red O staining revealed the significant reduction of fat accumulation (P<0.05) and the dFP::LGG labeled worms showed the promotion of autophagy. Additionally, the whole transcript sequencing and gene set variation analysis algorithm suggested that Nar improved the lipid biosynthesis and metabolism pathways, as well as the TGF-β, Wnt and longevity signaling pathway. The PPI network was applied to screen out hub genes in the above-mentioned pathways for further analysis. The expression levels of hub genes fat-7 and ech-6 were down-regulated, as well as aak-2, nhr-49, acs-2, hlh-30, lgg-1, unc-51, pha-4, skn-1 and yap-1 were up-regulated. Then, mutant worms and RNA interference were used to study the mechanism. It revealed that suppression of the expression of autophagy related genes including hlh-30, lgg-1, unc-51, pha-4, skn-1 and yap-1 could disable the fat-lowering, lifespan-prolonging, and health-promoting properties of Nar. Finally, a competing endogenous RNAs network was constructed to profoundly understand the beneficial mechanism caused by Nar. Conclusions: our findings elucidate that Nar plays the important role to alleviate HGI aging and anti-obesity effects by reducing fat accumulation and promoting autophagy.
