Metabolic disorders such as insulin resistance (IR) and dyslipidemia (DL) might contribute to the induction of diabetic cardiomyopathy
(DCM). However, few relevant animal models are currently available for studying the time-course of DCM and evaluating
experimental therapeutics. The present study proposes a rodent model of dietary-induced IR combined or not with DL in order to investigate
the impact of chronic IR and DL on in vivo myocardial function. Male rats were fed a western-type diet (65% fat; 15% fructose;
WD). DL was induced by combining the western diet with i.p. injections of a nonionic surface-active agent (P-407; 0.2 mg/kg, 3
times/wk; P-407). A chow diet was used as control. At 11 and 14 weeks, cardiac function was assessed by echocardiography. Fasting
blood glucose increased in WD group while plasma lipids markedly accumulated in P-407 treated rats. Echocardiographic data showed
no significant difference in cardiac geometry under basal conditions. Diastolic dysfunction was evidenced at 14 weeks by a significant
decrease in E/A ratio in the P-407 group. Moreover, fractional shortening was significantly depressed under dobutamine stress in WD
group at 14 weeks whereas systolic dysfunction appeared as early as 11 weeks and worsened at 14 weeks in P-407 animals. Finally, myocardial
TNF-alpha tissue content increased in P-407 group. In conclusion, DL exacerbated cardiac lipotoxicity and functional complications
associated with IR. This experimental model of combined IR and DL closely mimics the main clinical manifestations of DCM and
might therefore constitute a useful tool for the evaluation of pharmacological treatments.
Keywords: Dyslipidemia, insulin-resistance, cardiac dysfunction, inflammation.
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