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Role of TLR-4 in the inflammatory response and insulin resistance in adipose tissue in a chronic nutritional overload

Abstract

The prevalence of obesity has increased over the last two decades, this increase has been attributed to changes in dietary habit of prevailing increase in fats and sugars. It is evident that obesity is a risk factor for cardiovascular disease and insulin resistance and the inflammatory process favors this context, but still is not very clear how the inflammatory process starts and its link to insulin resistance in the face of a nutrient overload. Therefore the objective of this study will test the hypothesis that an increased burden will result in nutritional increased expression of toll like receptor 4 (TLR-4) and that starts the inflammatory response with consequent insulin resistance. For that will be used male Wistar rats (n = 90), 30 days old. The animals are randomly divided to receive control diet (C) or high calorie (H) for 6, 12 and 24 weeks, totaling six independent experimental groups (C6, C12, C24, H6, H12, H24, n = 15 animals / group). The mice receive C standard rodent chow (RC Focus 1765, Agroceres ®, Rio Claro, São Paulo, Brazil) and a group H calorie diet, consisting of: powder feed (CR 1765 Focus, Agroceres ®, Rio Claro, São Paulo, Brazil), processed foods, palm oil, protein supplements, vitamin and mineral mix, in addition, the animals of group H will also receive the addition of 300 g of sucrose in the drinking water offers will be food and water ad libitum. The consumption of diet and caloric intake will be checked every day, the caloric intake will be determined by the product of consumption and energy content of diets. Body weight is measured weekly and the rest of the evaluations will be performed in 6, 12 and 24 weeks. The index of adiposity is used as an indicator of obesity, the assessment of comorbidity are high blood pressure, glucose and lipid profile, hormonal evaluation, inflammation in the blood. In adipose tissue will be assessed indicators of inflammation among them tumor necrosis factor-alpha (TNF-±), interleukin -6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and transcriptional factors and IKK² NFkB, Toll like receptor 4 and IRS-1 total and phosphorylated. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PIERINE, D. T.; NAVARRO, M. E. L.; MINATEL, I. O.; LUVIZOTTO, R. A. M.; NASCIMENTO, A. F.; FERREIRA, A. L. A.; YEUM, K-J; CORREA, C. R.. Lycopene supplementation reduces TNF-alpha via RAGE in the kidney of obese rats. NUTRITION & DIABETES, v. 4, . (11/14132-0, 10/06100-9)
MARIA EUGÊNIA LOPES NAVARRO; KLINSMANN CAROLO DOS SANTOS; ANDRÉ FERREIRA DO NASCIMENTO; FABIANE VALENTINI FRANCISQUETI; IGOR OTÁVIO MINATEL; DAMIANA TORTOLERO PIERINE; RENATA AZEVEDO DE MELO LUVIZOTTO; ANA LÚCIA A. FERREIRA; DIJON HENRIQUE SALOMÉ DE CAMPOS; CAMILA RENATA CORRÊA. Inflamação renal, alterações metabólicas e oxidativas após 6 semanas de dieta de cafeteria em ratos. J. Bras. Nefrol., v. 38, n. 1, p. 9-14, . (11/14132-0)
FRANCISQUETI, FABIANE VALENTINI; NASCIMENTO, ANDRE FERREIRA; MINATEL, IGOR OTAVIO; DIAS, MARCOS CORREA; MELO LUVIZOTTO, RENATA DE AZEVEDO; BERCHIERI-RONCHI, CAROLINA; FERREIRA, ANA LUCIA A.; CORREA, CAMILA RENATA. Metabolic syndrome and inflammation in adipose tissue occur at different times in animals submitted to a high-sugar/fat diet. JOURNAL OF NUTRITIONAL SCIENCE, v. 6, . (11/14132-0, 11/14593-8, 15/10626-0)