Gamma oryzanol modulates hepatic lipids expression and regulates integrated pathways in liver disease pathophysiology under a high sugar fat diet.

Diets high in simple carbohydrates and saturated fats increase the risk of liver diseases. Gamma oryzanol (ORY), a compound found in rice bran, shows promise in addressing metabolic liver diseases, though its impact on lipid pathways requires further exploration. This study evaluated the effects of ORY in rats submitted to a high sugar-fat (HSF) diet using a multiomics approach to unravel its impact on lipid metabolism and associated pathways. Male Wistar rats were fed a control (CTRL), HSF, or HSF + ORY (0.5% w/w) diet for 30 weeks. Hepatic lipid profiling was performed using high-resolution mass spectrometry. Proteins and lipids were integrated into molecular pathway analyses. miR-122 expression was assessed by qRT-PCR, while oxidative stress markers were measured via colorimetric assays. The HSF diet altered 233 lipids compared to CTRL, while ORY supplementation modulated 84 lipids relative to the HSF group, with 39 lipids showing opposing regulatory profiles. Integrating proteomic data revealed key pathways in MAFLD pathophysiology affected by ORY. Additionally, ORY regulated miR-122 expression linked to lipid metabolism and reduced oxidative stress, demonstrating its potential to mitigate HSF-induced liver damage. ORY modulates hepatic lipid profiles and influences integrated metabolic networks, suggesting a significant role in MAFLD prevention and treatment.