High fructose intake promotes hepatic lipid accumulation. Pterostilbene, a natural analogue of resveratrol found in diet berries, exhibits a hepatoprotective property. Here, we studied the protection by pterostilbene against fructose-induced hepatic lipid accumulation and explored its possible mechanism. We observed a high expression of microRNA-34a (miR-34a, P < 0.05) and a low expression of its target, sirtuin1 (Sirt1, mRNA: P < 0.01; protein: P < 0.001), with the overactivation 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 the fructose-disturbed miR-34a expression (0.3-0.5-fold vs fructose control, P < 0.05), Sirt1 protein level (1.2- to 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 triglyceride and total cholesterol (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 the anti-lipogenic effect of pterostilbene against fructose-induced hepatic lipid accumulation via modulating the miR-34a/Sirt1/SREBP-1 pathway.
Keywords: Sirt1/SREBP-1 pathway; fructose; hepatic lipid accumulation; miR-34a; pterostilbene.