A high-sucrose diet exacerbates the left ventricular phenotype in a high fat-fed streptozotocin rat model of diabetic cardiomyopathy

Abstract

Left ventricular (LV) dysfunction is an early, clinically detectable sign of cardiomyopathy in type 2 diabetes mellitus (T2DM) that precedes the development of symptomatic heart failure. Pre-clinical models of diabetic cardiomyopathy are essential to develop therapies that may prevent or delay the progression of heart failure. This study examined the molecular, structural, and functional cardiac phenotype of two rat models of T2DM induced by a high-fat diet (HFD) with a moderate- or high-sucrose content (containing 88.9 or 346 g/Kg sucrose, respectively), plus administration of low-dose streptozotocin (STZ). At eight weeks of age, male Sprague-Dawley rats commenced a moderate- or high-sucrose HFD. Two weeks later, rats received low-dose STZ (35 mg/kg i.p. for two days) and remained on their respective diets. LV function was assessed by echocardiography one week prior to endpoint. At 22 weeks of age, blood and tissues were collected post-mortem. Relative to chow-fed sham rats, diabetic rats on a moderate- or high-sucrose HFD displayed cardiac reactive oxygen species dysregulation, perivascular fibrosis, and impaired LV diastolic function. The diabetes-induced impact on LV adverse remodeling and diastolic dysfunction was more apparent when a high-sucrose HFD was superimposed on STZ. In conclusion, a high-sucrose HFD in combination with low-dose STZ produced a cardiac phenotype that more closely resembled T2DM-induced cardiomyopathy than STZ diabetic rats subjected to a moderate-sucrose HFD.

Moderate- and High-Intensity Endurance Training Alleviate Diabetes-Induced Cardiac Dysfunction in Rats

“…Although not yet extensively studied, dietary interventions high in monosaccharide fructose caused insulin resistance, unchanged or mildly elevated blood glucose, dyslipidemia and notable diastolic function in rodents [ 55 , 56 , 57 ]. Velagic et al demonstrated that cardiac complications were more advanced in STZ-induced diabetic rats on a high-sugar HFD compared with those on a moderate-sugar HFD for 8 weeks, indicating the crucial role of sugars in diet composition in preclinical models for diabetic heart diseases [ 58 ]. Furthermore, elevated myocardial fructose has been shown to be an early cardiac response to diabetes, preceding clinically-detected diastolic dysfunction [ 59 , 60 ].…”

Moderate-Intensity and High-Intensity Interval Exercise Training Offer Equal Cardioprotection, with Different Mechanisms, during the Development of Type 2 Diabetes in Rats

“…Preclinically, diets high in both fat and sucrose have been shown to induce T2DM with LV hypertrophy and diastolic dysfunction in mice after 16 weeks and 17 weeks, respectively [26,27]. Following injection with a pancreatic β-cell toxin, rats that were fed a high-sucrose, HFD displayed worse adverse LV remodeling and diastolic dysfunction compared with moderate-sucrose, HFD-fed rats [28]. To mimic this clinical situation, our research group previously developed a rat model of T2DM induced by a high-sucrose diet or the WD, with adverse cardiac remodeling and cardiac dysfunction [19].…”