The antihyperlipidemic effects of fullerenol nanoparticles via adjusting the gut microbiota in vivo.

BACKGROUND: Nanoparticles (NPs) administered orally will meet the gut microbiota, but their impacts on microbiota homeostasis and the consequent physiological relevance remain largely unknown. Here, we describe the modulatory effects and the consequent pharmacological outputs of two orally administered fullerenols NPs (Fol1 C60(OH)7(O)8 and Fol113 C60(OH)11(O)6) on gut microbiota. RESULTS: Administration of Fol1 and Fol113 NPs for 4 weeks largely shifted the overall structure of gut microbiota in mice. The bacteria belonging to putative short-chain fatty acids (SCFAs)-producing genera were markedly increased by both NPs, especially Fol1. Dynamic analysis showed that major SCFAs-producers and key butyrate-producing gene were significantly enriched after treatment for 7-28 days. The fecal contents of SCFAs were consequently increased, which was accompanied by significant decreases of triglycerides and total cholesterol levels in the blood and liver, with Fol1 superior to Fol113. Under cultivation in vitro, fullerenols NPs can be degraded by gut flora and exhibited a similar capacity of inulin to promote SCFA-producing genera. The differential effects of Fol1 and Fol113 NPs on the microbiome may be attributable to their subtly varied surface structures. CONCLUSIONS: The two fullerenol NPs remarkably modulate the gut microbiota and selectively enrich SCFA-producing bacteria, which may be an important reason for their anti-hyperlipidemic effect in mice.

Syringaresinol-4-O-ß-d-glucoside alters lipid and glucose metabolism in HepG2 cells and C2C12 myotubes.

Syringaresinol-4-O-ß-d-glucoside (SSG), a furofuran-type lignan, was found to modulate lipid and glucose metabolism through an activity screen of lipid accumulation and glucose consumption, and was therefore considered as a promising candidate for the prevention and treatment of metabolic disorder, especially in lipid and glucose metabolic homeostasis. In this study, the effects of SSG on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were further investigated. Treatment with SSG significantly inhibited lipid accumulation by oil red O staining and reduced the intracellular contents of total lipid, cholesterol and triglyceride in HepG2 cells. No effect was observed on cell viability in the MTT assay at concentrations of 0.1-10 µmol/L. SSG also increased glucose consumption by HepG2 cells and glucose uptake by C2C12 myotubes. Furthermore, real-time quantitative PCR revealed that the beneficial effects were associated with the down-regulation of sterol regulatory element-binding proteins-1c, -2 (SREBP-1c, -2), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC) and hydroxyl methylglutaryl CoA reductase (HMGR), and up-regulation of peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ). SSG also significantly elevated transcription activity of PPARγ tested by luciferase assay. These results suggest that SSG is an effective regulator of lipogenesis and glucose consumption and might be a candidate for further research in the prevention and treatment of lipid and glucose metabolic diseases.