High-fat but not normal-fat intake of extra virgin olive oil modulates the liver proteome of mice

Purpose The metabolic benefits of the Mediterranean diet have been largely attributed to its olive oil content. Whether the ingested fat amount is relevant to these effects is not clear. We thus compared the effects of high-fat and normal-fat intake of extra-virgin olive oil (EVOO) on the liver proteome. Methods Three groups of mice were fed for 12 weeks with either normal-fat diets containing either soybean oil (control, C) or EVOO (NO) or a high-fat EVOO diet (HO). Body weight and food intake were measured weekly and serum parameters were analyzed. The liver was processed for data-independent acquisition mass spectrometry-based proteomics. The differentially expressed proteins among the groups were submitted to pathway enrichment analysis. Results The consumption of HO diet reduced food intake and serum triglycerides, while it preserved body weight gain, adiposity, and glycemia. However, it increased serum cholesterol and liver mass. The proteomic analysis showed 98 altered proteins, which were allocated in 27 significantly enriched pathways. The pathway analysis suggested stimulation of mitochondrial and peroxissomal beta-oxidation, and inhibition of lipid synthesis and gluconeogenesis in the HO group. Although the NO group failed to show significant liver proteome alterations, it presented reduced body fat, body weight gain, and serum triglycerides and glucose levels. Conclusion The data indicate that the intake of the HO diet induced hepatic adjustments, which were partially successful in counteracting the detrimental outcomes of a high-fat feeding. Contrastingly, the NO diet had beneficial effects which were not accompanied by significant modifications on hepatic proteome.