Pterostilbene improves hepatic lipid accumulation via the MiR-34a/Sirt1/SREBP-1 pathway in fructose-fed rats. - GreenMedInfo Summary
Pterostilbene Improves Hepatic Lipid Accumulation via the MiR-34a/Sirt1/SREBP-1 Pathway in Fructose-Fed Rats.
J Agric Food Chem. 2020 Jan 12. Epub 2020 Jan 12. PMID: 31927917
Wen-Yuan Wu
High fructose intake promotes hepatic lipid accumulation. Pterostilbene, a natural analogue of resveratrol enriched in diet berries, exhibits hepatoprotective property. Here, we studied the protection by pterostilbene against fructose-induced hepatic lipid accumulation, and explored its possible mechanism. We observed high-expression of microRNA-34a (miR-34a, P<0.05) and low-expression of its target sirtuin1 (Sirt1, mRNA: P<0.01; protein: P<0.001), with over-activation of downstream sterol regulatory element-binding protein-1 (SREBP-1) lipogenic pathway (nuclear SREBP-1 protein: P<0.05; FAS and SCD1 mRNA: P<0.01), in rat livers, as well as BRL-3A and HepG2 cells, stimulated by fructose. More interestingly, pterostilbene recovered fructose-disturbed miR-34a expression (0.3-0.5 fold vs. fructose control, P<0.05), Sirt1 protein level (1.2-1.5 fold vs. fructose control, P<0.05) and SREBP-1 lipogenic pathway, resulting in significant amelioration of hepatocyte lipid accumulation in animal (Hepatic TG&TC mg/g·wet tissue: 4.90 ± 0.19, 5.23 ± 0.16, 5.20 ± 0.29 vs. fructose control 9.73 ± 1.06, P<0.001; 3.18± 0.30, 3.31 ± 0.39, 3.37 ± 0.47 vs. 5.67 ± 0.28, P<0.001) and cell models (BRL-3A TG&TC mmol/g·protein: 0.123 ± 0.011 vs. 0.177 ± 0.004, P<0.001; 0.169± 0.011 vs. 0.202 ± 0.008, P<0.05; HepG2: 0.257± 0.005 vs. 0.303 ± 0.016, P<0.05; 0.143± 0.004 vs. 0.201 ± 0.008, P<0.001). These results provide the experimental evidence supporting anti-lipogenic effect of pterostilbene against fructose-induced hepatic lipid accumulation via modulating the miR-34a/Sirt1/SREBP-1 pathway.