AT1 Receptor Blockade Attenuates Insulin Resistance and Myocardial Remodeling in Rats with Diet-Induced Obesity

Autor(es)

Oliveira-Junior, Silvio A. ^{[1, 2]} ; Martinez, Paula F. ^{[1, 2]} ; Guizoni, Danielle M. ^[1] ; Campos, Dijon H. S. ^[1] ; Fernandes, Tiago ^[3] ; Oliveira, Edilamar M. ^[3] ; Okoshi, Marina P. ^[1] ; Okoshi, Katashi ^[1] ; Padovani, Carlos R. ^[4] ; Cicogna, Antonio C. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Botucatu Med Sch, Botucatu, SP - Brazil

^[2] Univ Fed Mato Grosso do Sul, Sch Physiotherapy, Campo Grande - Brazil

^[3] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo - Brazil

^[4] Sao Paulo State Univ, Botucatu Biosci Inst, Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 9, n. 1 JAN 23 2014.
• Citações Web of Science: 23

Resumo

Background: Although obesity has been associated with metabolic and cardiac disturbances, the carrier mechanisms for these responses are poorly understood. This study analyzed whether angiotensin II blockade attenuates metabolic and cardiovascular disorders in rats with diet-induced obesity. Material and Methods: Wistar-Kyoto (n = 40) rats were subjected to control (C; 3.2 kcal/g) and hypercaloric diets (OB; 4.6 kcal/g) for 30 weeks. Subsequently, rats were distributed to four groups: C, CL, OB, and OBL. L groups received Losartan (30 mg/kg/day) for five weeks. After this period we performed in vivo glucose tolerance and insulin tolerance tests, and measured triacylglycerol, insulin, angiotensin-converting enzyme activity (ACE), and leptin levels. Cardiovascular analyzes included systolic blood pressure (SBP), echocardiography, myocardial morphometric study, myosin heavy chain composition, and measurements of myocardial protein levels of angiotensin, extracellular signal-regulated (ERK1/2), c-Jun amino-terminal kinases (JNK), insulin receptor subunit beta (beta IR), and phosphatidylinositol 3-kinase (PI3K) by Western Blot. Results: Glucose metabolism, insulin, lipid, and ACE activity disorders observed with obesity were minimized by Losartan. Moreover, obesity was associated with increased SBP, myocardial hypertrophy, interstitial fibrosis and improved systolic performance; these effects were also minimized with Losartan. On a molecular level, OB exhibited higher ERK, Tyr-phosphorylated beta IR, and PI3K expression, and reduced myocardial angiotensin and JNK expression. ERK and JNK expression were regulated in the presence of Losartan, while angiotensin, Tyr-beta RI, total and Tyr-phosphorylated PI3K expression were elevated in the OBL group. Conclusion: Angiotensin II blockade with Losartan attenuates obesity-induced metabolic and cardiovascular changes. (AU)

• Processo FAPESP: 08/55339-4 - Participação da angiotensina II na remodelação e resistência a insulina no miocárdio de ratos obesos
• Beneficiário: Antonio Carlos Cicogna
• Modalidade de apoio: Auxílio à Pesquisa - Regular