Effect of the high-fat diet and yerba mate aqueous extract intake (Ilex paraguariensis) on the expression of proteins involved in the inflammatory response and insulin signaling regulation in the liver of Wistar rats

Introduction Obesity is associated with a chronic low-grade inflammation that predisposes to insulin resistance and to the development of type 2 diabetes. The augmentation of plasmatic nonesterified fatty acids and proinflammatory cytokines increases the hepatic expression of some kinases (inhibitor of kappa B kinase (IKK-) and c-jun N-terminal kinase (JNK)) that increases the inflammatory response and impairs the insulin signaling. Yerba mate (Ilex paraguariensis) contains bioactive compounds, which have the ability to reduce the expression of genes involved in inflammatory response. Objective This aim of this project was to investigate the effect of yerba mate aqueous extract (YMAE) intake on the inflammatory response and insulin signaling regulation in the liver of Wistar rats submitted to adjusted high-fat diet (HFD). Methods Male Wistar rats were fed with a control diet (n=18) or a HFD (n=18) for 12 weeks. After this, six animals of each group were euthanized and the rest of the animals were distributed in groups that received, or not, by gavage, YMAE (1g/kg body weight/day) for four weeks. Then, all the animals were euthanized and was determined the glucose, insulin, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, triacylglycerol (TAG), leptin, adiponectin, TNF-, IL-6, C-reactive protein (CPR), plasminogen activator inhibitor (PAI)-1 and MCP-1 concentration, and the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) plasma activity. Histological analysis was performed for the evaluation of lipid infiltration. The body composition of the animal was also evaluated. To expression evaluation of the JNK, IKK-, NF-B, IRS-1 and AKT, a group of animals (n = 36) underwent the same experimental protocol, however, insulin infusion were done previously to moment of euthanasia. All animal were submitted to the oral glucose tolerance test (oGTT) and the intraperitoneal insulin tolerance test (ipITT) in the first, twelfth and sixteenth weeks of the experimental protocol. Results After 12 weeks of experimental protocol, HLBL group had higher feed intake, however, isocaloric intake when compared to the CONBL group (p < 0,05). The HLBL group had a significant increase of weight gain; retroperitoneal adipose deposit and liver weight; fasting glycaemia; glycaemia when submitted to oGTT in all times of the test and upon ipITT at time 0, 5, 30 and 40; serum total cholesterol, LDLcholesterol; PAI-1 and CRP in relation to CONBL (p < 0.05). Only one third of the HLBL animals presented micro and macrogoticular discrete degeneration. The consumption of HFD decreased the hepatic AKT phosphorylation compared to animals fed with the CON diet (p < 0,05). As regards to the YMAE effects, it was observed that this intervention did not alters food consumption, because the animals submitted to the HFD, with or without YMAE administration, ingested significantly lower quantity in relation to their respective control groups (p < 0.05). However, energy consumption again proved to be isocaloric (p < 0.05). The administration of YMAE reversed the weight gain in the groups fed with HFD and also reduced the percentage of carcass fat in the animals fed with the CON diet in relation to the respective groups without intervention (p < 0.05). The CONEM group presented an increased percentage of lean mass and reduction in blood glucose concentration in the ipITT after 5 and 10 minutes from the beginning of the test when compared to the control group (p < 0.05). The YMAE reduced serum total cholesterol concentration in the group fed with the HFD compared to CON group (p < 0,05). The HLEM group presented lowest ratio of expression of phosphorylated by total IKK-, NFB phosphorylation, as well as the major ratio of the expression of phosphorylated by total AKT than HFD group (p < 0,05). Conclusions HFD intake induced liver proinflammatory profile and glucose intolerance. Thus, HFD intake can be considered a relevant factor in the etiology of obesity and the development of chronic non-comunicable diseases, in particular, the type 2 diabetes. The intervention with YMAE modulates the inflammatory response and decreased glucose intolerance. All these factors together indicate that yerba mate may have a positive effect on risk reduction and treatment of chronic diseases. (AU)