Olive oil and oleate affect hepatic proteome and mitochondrial dynamics: in vivo and in vitro approaches

The Mediterranean diet (MD) has been pointed out as a nutritional approach to prevent metabolic disturbances leading to obesity, diabetes and liver steatosis. These properties have been largely attributed to oleic acid and polyphenol compounds present in olive oil (OO), the main fat source of MD. However, there are controversies regarding the consequences of excessive extra virgin olive oil (EVOO) intake. Prolonged high-fat feeding may induce obesity, insulin resistance, and non-alcoholic fatty liver disease. Dysfunction of mitochondrial dynamics along with endoplasmic reticulum (ER) stress, have been suggested to play a role in the establishment of these disturbances. The mechanism seems to involve a prevalence of the fission process over the fusion process, and endoplasmic reticulum stress, with activation of the unfolded protein response (UPR) and consequent stimulation of inflammatory pathways. The dietary fats differ in their lipotocixity degree, with saturated fatty acids being considered more harmful, while the monounsaturated oleic acid has been suggested to protect against lipotoxicity. However, data on the mechanisms involved as well as on the existence of a dose-dependency are not conclusive. Given that the liver is a key organ for the maintenance of the metabolic homeostasis and is highly susceptible to dietary manipulations, focusing on the consequences of high-fat feeding on this tissue is of relevance. With the aim of evaluating these aspects, we used both in vivo and in vitro approaches. The animal study examined body, serum, and hepatic parameters after the prolonged intake of diets containing either normolipidic or hyperlipidic amounts of EVOO. To perform a broad analysis of liver metabolism, a proteomic approach was used. Two months-old swiss mice were fed for 12 weeks with either normolipidic diets (9.5% energy from fat) containing soy oil (control diet, C) or EVOO (NO diet) or a high fat EVOO diet (HO, 39% energy from fat). Body weight and food intake were measured weekly and serum parameters were analyzed by enzymatic methods. Liver proteome was analyzed by LC-MS/MS and the proteomic data were analyzed by one-way Anova followed by Tukey post-hoc and Benjamini-Hochberg correction. Pathway enrichment analysis was performed with Fisher´s test and corrected by the Bonferroni approach. ... [edited by Author]