Ricerc@Sapienza

Oxidative stress and inflammation play a role in
the physiopathology of insulin resistance, diabetes and cardio-
vascular disease. A single high-fat, high-carbohydrate (HFHC)
meal induces an increase in inflammatory and oxidative
stress markers in peripheral blood mononuclear cells (PBMC).
Previous studies have shown that orange juice is able to prevent
this response by inhibiting toll like receptors (TLR) expression
and endotoxemia. Our goal was to study the proteome response
in PBMC after the consumption of a HFHC meal consumed
with water, orange juice or an isocaloric beverage (water with
glucose). Twelve healthy individuals completed the protocol
in a crossover design, and blood samples were obtained before
and 1, 3, and 5 h after consumption. Proteomic profile, glucose,
insulin, lipid and cytokines levels were investigated. The glycemic and insulinemic response was higher when the meal was consumed with glucose, while there was no difference in the response between water and orange juice. Proteome analysis in PBMC was carried out using TMT ten-plex. A total of 3813 proteins, originating from 15 662 peptides were identified. Three proteins showed significantly altered expression in the three treatments: apolipoprotein A-II, ceruloplasmin and hemopexin. When the HFHC meal was consumed with water there was an increase in some inflammatory pathways such as the Fc-gamma receptor dependent phagocytosis and the complement cascade, but the immune system as a whole was not signif- icantly altered. However, when the meal was consumed with glucose, the immune system was up regulated. Among the pathways induced after 3 h were those of the adaptive immune system and cytokine signaling. Five hours after the meal, pathways of the complement cascade and classical antibody mediated complement activation were up regulated. When the meal was consumed with orange juice there was an up regulation of proteins involved in signal transduction, DNA replication and cell cycle. The promyelocytic leukemia protein (PML) showed a 28.2-fold increase. This protein was down regulated when the meal was consumed with water. Regarding the immune system, several of the pathways induced by glucose were down regulated when the meal was consumed with orange juice: proteins involved with the adaptive immune system and cytokine signaling. Therefore, we have shown that orange juice can not only suppress diet induced inflammation, but also regulate the expression of proteins such as PML, which may play a key role in the regulation of metabolism.