Comparative lipidomic and transcriptomic analyses reveal distinct regulatory effects of tree nut oils on hepatic lipid metabolism in high-fat diet-fed mice

Tree nut oils from the Juglandaceae family are rich in unsaturated fatty acids and bioactive components, yet their metabolic effects under high-fat diet (HFD) conditions remain incompletely understood. This study compared the effects of walnut, pecan, hickory, and soybean oils in HFD-fed mice using integrated lipidomic and transcriptomic analyses. The oil interventions showed differential effects on plasma and hepatic lipid metabolism, with all four oils significantly reducing plasma total cholesterol. Lipidomic profiling identified 1324 lipid species and revealed distinct remodeling of HFD-altered hepatic lipids, with walnut oil significantly reducing hepatic cholesteryl ester levels. Transcriptomic analysis revealed distinct transcriptional patterns associated with lipid metabolism and inflammatory responses among the oil interventions. RT-qPCR further showed that walnut and hickory oils significantly reduced Cd36 expression, while all tree nut oils significantly reduced Srebf1 expression. Collectively, these findings indicate that tree nut oils exert distinct metabolic effects under HFD conditions, accompanied by differential hepatic lipidomic and transcriptional responses, with implications for the nutritional evaluation of plant-derived oils.