Hepatoprotective mechanisms of pomegranate bioactives on a murine models affected by NAFLD as analysed by MS-based proteomics: The mitochondria in the eye of the storm.

Deciphering the mechanisms underlying the direct association between fructose consumption and the onset and progression of non-alcoholic fatty liver disease (NAFLD), as well as the high prevalence of metabolic syndrome (MetS), is of great importance for adopting potential nutritional strategies. Thus, an evaluation of the impact of sustained high fructose consumption on the liver physiology of Wistar rats was made. Moreover, the effectiveness of a dietary pomegranate-derived supplement (P) at counteracting fructose-induced liver injury was also assessed. For unveiling the underlying mechanisms, an untargeted proteomic analysis of the livers from nineteen Wistar rats fed on a basal commercial feed and supplemented with either drinking water (C) (n = 6), 30 % (w/v) fructose in drinking water (F) (n = 7) or 30 % (w/v) fructose solution plus 0.2 % (w/v) P (F+P) (n = 6) was assessed. Fructose intake severely increased the abundance of several energy-production related-proteins, such as fructose-bisphosphate aldolase or fatty acid synthase, among others, as well as diminished the amount of another ones, such as carnitine O-palmitoyl transferase or different subunits of acyl-coenzyme A oxidase. These changes could facilitate mitochondrial disturbances and oxidative stress. Regarding the hepatic proteome of F, P extract restored mitochondrial homeostasis and strengthened endogenous antioxidant mechanisms diminishing the amount of proteins involved in process that could increase the oxidative status, as well as increasing both the quantity of several proteins involved in proteasome functionality, as expressing changes in the amount of certain RNA-splicing related-proteins, regarding F proteome.