Mitigative effects of the bioactive flavonol fisetin on high-fat/high-sucrose induced nonalcoholic fatty liver disease in rats.

Abstract

Worldwide growing rates of obesity are correlated with the rising prevalence of nonalcoholic fatty liver disease (NAFLD) with limited available therapeutics. The present study was undertaken to investigate the modulatory effects of dietary supplementation fisetin on hepatocyte nuclear factor 4 α (HNF4α) gene expression, hepatic lipin-1 signaling, thioredoxin-interacting protein (TXNIP) levels, poly-(ADP-ribose)-polymerase-1 (PARP-1) activity, as well as some oxidative stress parameters in a rat model of high-fat/high-sucrose (HFHS) induced NAFLD. Sixty male albino rats were allocated into four equal groups: normal control group, fisetin-treated control group, NAFLD group, and fisetin-treated NAFLD group. Gene expression levels of HNF4-α were estimated using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), while Lipin-1, TXNIP levels, and PARP-1 activity were estimated by enzyme-linked immunosorbent assay (ELISA); lipid profile, hepatic lipid contents, hepatic lipoperoxides, fatty acid synthase activity, and total antioxidant capacity were also assessed colorimetrically. Fisetin ameliorated HFHS-induced NAFLD; where it suppressed hepatic lipid accumulation, upregulated HNF4-α /lipin-1 signaling, mitigated oxidative stress, inhibited reactive oxygen species (ROS)-mediated TXNIP induction, and PARP-1 activation . In conclusion, fisetin could confer protection against NAFLD and impede its progression. However,additional experimental scrutiny is needed to verify these findings.