Cardiovascular Function in a Rat Model of Diet-Induced Obesity

Abstract

Abstract-The obesity-prone/obesity-resistant rat model has been used to study mechanisms responsible for obesity-related abnormalities in renal function and blood pressure, but whether this model exhibits cardiac dysfunction has not been determined. We tested the hypothesis that obesity-prone rats would display cardiovascular abnormalities seen in other diet-induced obese models (ie, hypertension, tachycardia, left ventricular hypertrophy, increased collagen deposition, reduced cardiac contractility, and increased end diastolic pressure). Male Sprague-Dawley rats were fed a control diet or a moderate fat diet containing 32% kcal as fat while hemodynamics were continuously monitored using telemetry. After 12 weeks, obesity-prone rats were significantly heavier and had greater body fat compared with obesity-resistant rats and controls, but daily (20 hours/d) averages and diurnal rhythms of blood pressure and heart rate did not differ among groups. Echocardiographic indices of cardiac structure and function, histological evidence of cardiac collagen, and directly measured heart weights did not differ among groups. Peak left ventricular pressure, end diastolic pressure, ϩdP/dt, and ϪdP/dt were also not significantly different among groups. Plasma cholesterol and hepatic cholesterol were significantly higher in obesity-prone rats compared with obesity-resistant rats and controls; hepatic triglycerides were higher in obesity-prone rats compared with controls (PՅ0.05). Leptin was significantly higher in obesity-prone rats compared with controls and across all groups was significantly correlated with body fat (PՅ0.05). These results suggest that 12 weeks of a moderate fat diet in the obesity-prone/obesity-resistant rat model induced lipid and endocrine abnormalities typical of obesity but was not sufficient to cause significant cardiac abnormalities. Key Words: hypertrophy Ⅲ echocardiography Ⅲ blood pressure Ⅲ cardiac output Ⅲ rats Ⅲ diurnal rhythm T he prevalence of obesity in the United States has increased in the last several decades, with two-thirds of Americans now considered overweight or obese. 1,2 Obesity decreases life expectancy and increases the incidence of stroke and coronary heart disease. 3 Elucidating mechanisms involved in obesityrelated cardiac dysfunction requires use of appropriate animal models. Genetic models of obesity in rodents such as the ob/ob rat, the Zucker obese rat. and the spontaneously hypertensive obese rat have been used for cardiovascular research. 4,5 However, these models may not exhibit the same abnormalities as do obese humans, such as hypertension, hyperglycemia, hyperinsulinemia, and cardiac hypertrophy. 4,6 In contrast, diet-induced models of obesity in the dog and rabbit have shown promise for studying cardiovascular 7-9 and renal 10 mechanisms involved in obesity-related pathologies.There is little doubt that a rodent model of obesity based on the intake of a high-fat diet would be advantageous in studying obesity-related cardiovascular abnormalities. One such model that has ...

Effect of high-fat diet feeding on hypothalamic redox signaling and central blood pressure regulation

“…25 Therefore, in this study, we decided to test whether blood pressure, measured in freely moving obesity-prone rats, can be increased by a diet with higher fat content (60% of total calorie), fed for a longer period (24 weeks) compared with the 32% HF diet fed for 10-12 weeks in earlier rat studies. [21][22][23] This diet treatment led to significantly elevated body weight and dyslipidemia; however, the plasma insulin and glucose levels were not elevated compared with chow-fed rats. This could be because both our control and HF diet-fed rats were selectively bred obesity-prone rats that show signs of metabolic syndrome even when fed with regular chow.…”

“…Although some studies reported significant increases in blood pressure using tail cuff measurements, 21,22 others that used telemetry showed no change. 23 In addition, the question was raised that higher blood pressure values measured with tail cuff in HFfed animals were the result of an augmented stress response to restraint accompanying this blood pressure measurement procedure. This explanation is supported by those findings where obesity leads to amplified and longer lasting cardiovascular stress responses in obese Zucker rats 24 and in spontaneously hypertensive rats fed with an HF diet.…”

Cardiac remodeling and diastolic dysfunction in DahlS.Z-Leprfa/Leprfa rats: a new animal model of metabolic syndrome

“…A diet with a moderate fat content was found to induce metabolic abnormalities but did not result in LV diastolic dysfunction in obesity-prone Sprague-Dawley rats. 7 On the other hand, the SHR (spontaneously hypertensive rat)/ NDmcr-cp rat, a genetic model of MetS that is a derivative of the SHR with deficiency of the leptin receptor, was shown to develop severe hypertension and LV diastolic dysfunction as well as LV hypertrophy and coronary perivascular fibrosis when fed a high-salt diet. 8 We recently established a new animal model of MetS, the DahlS.Z-Lepr fa / Lepr fa (Dahl salt-sensitive (DS)/obese) rat, by crossing DS rats and Zucker rats with a missense mutation in the leptin receptor gene (Lepr).…”

An experimental study to see the antihypertensive effects of gymnema sylvestre and acorus calamus in wistar rats and its comparison with amlodipine

“…HFD fed rats can act as a 'humanized' model for obesity and its related co-morbidities. 13,14 In the present study obesity and hypertension was induced in rats by feeding them on diet rich in fats. Systolic blood pressure increased significantly in rats fed on HFD as compared to the normal control group.…”