Myocardial structure, function and ischaemic tolerance in a rodent model of obesity with insulin resistance

摘要: New findings • What is the central question of this study?Does obesity with insulin resistance decrease left ventricular pump function and/or myocardial tolerance to ischaemia in a rodent model metabolic syndrome, and what mechanisms are involved these changes? • What main finding its importance?These data suggest that although may be maintained resistance, hearts from animals more prone ischaemia–reperfusion injury, which part due changes functionality reperfusion injury salvage kinase (RISK) pathway. Interventions/therapies aimed at normalizing RISK pathway have potential normalize patients syndrome. Obesity comorbidities (dyslipidaemia, hypertension) together constitute syndrome all risk factors for ischaemic heart disease. Although has been reported an independent factor congestive failure, whether obesity-induced failure develops absence increased afterload (induced by not clear. We previously shown decreases ischaemia–reperfusion, but mechanism decreased remains unclear. hypothesize induces adverse cardiac remodelling dysfunction, as well prosurvival signalling reduce ischaemia–reperfusion. Wistar rats were fed obesogenic (obese group) or standard rat chow diet (control 32 weeks. Echocardiography was performed over weeks before isolated Langendorff-perfused subjected 40 min coronary artery ligation followed reperfusion, functional recovery (rate–pressure product), infarct size assessed (Western blot analysis). Obesity lipid accumulation had no effect on vivo ex structure/function. Hearts obese lower rate–pressure products (13115 ± 562 beats min−1 mmHg versus 17781 1109 control rats, P < 0.05) larger infarcts (36.3 5.6% area 14.1 2.8% 0.01) compared hearts. These associated reductions function, 30–50 40–60% Akt glycogen synthase 3 beta (GSK-3β) expression phosphorylation, respectively, Total endothelial nitric oxide reduced 25% rats. conclude basal structure This reduction likely compromised obese, insulin-resistant animals.