A reliable model of metabolic syndrome in rats

Abstract

Metabolic syndrome has become a major public-health challenge worldwide. Major cause is junk food associated with a genetic predisposition. The aim of this study was to characterize a model of metabolic syndrome induced by high-fat diet (HFD) in rats having a polygenic predisposition to develop obesity. Obese prone (OP) and obese resistant (OR) Sprague Dawley rats were respectively fed with a HFD and a standard diet (Std) for 16 weeks or 1year (4 groups, n = 10 per group). Feeding behaviour, caloric intake, body weight and systemic arterial pressure were weekly recorded. At the end of the protocol, abdominal obesity, glucose tolerance, lipidemia and blood pressure were compared between groups. Despite, their high calorie diet, OP rats showed a higher daily food consumption and calorie intake. Plasma leptin was increased in OP-HFD (5.8 ± 0.5 ng/ml versus 1 ± 0.5 ng/ml in OR-Std, P < 0.001) suggesting a leptin resistance. Calorie intake was stable over time in the 2 groups. In the short protocol (16 weeks), OP-HFD rats presented already increased total body and abdominal fat weights, glucose intolerance, and increased plasma concentration of total cholesterol, triglycerides and nHDL/HDL ratio. Despite an overtime increase in systolic arterial pressure in the OP-HFD group, left ventricular systolic pressure was not increased at 16 weeks (117 + 6 versus 111 + 8 in OR-Std, NS). In the long protocol (1 year), obesity and glucose intolerance were still present, fasting blood glucose being still unchanged compared to the OR-Std group. Dyslipidemia (total cholesterol, triglycerides and nHDL/HDL ratio) was exacerbated compared to the short protocol and OP-HFD developed systemic hypertension (164 ± 6 vs. 120 ± 5 mmHg, P = 0.001). One year of HFD in Sprague Dawley rats selected for their predisposition to obesity leads to a reliable metabolic syndrome characterized by abdominal obesity, glucose intolerance, dyslipidemia and hypertension.