Respective roles of genetic background and high fat diet in a rodent model of metabolic syndrome

Abstract

The metabolic syndrome is a worldwide public health problem. Major cause is the junk food associated with a genetic predisposition. To better understand the mechanisms it is imperative to develop animal models closest to human problem. Cardiometabolic alterations were studied in a polygenic rat model of metabolic syndrome. We therefore evaluated the respective roles of the substrain and the diet. Ten obese prone (OP), obese resistant (OR) and control (CTRL) Sprague–Dawley rats were fed with high fat (HF) or standard diet (SD) for 16 weeks. Feeding behaviour and criteria of the metabolic syndrome were determined. Arterial pressure was weekly recorded. Leptin and adiponectin were measured. CTRL and OR rats regulated their appetite to maintain a reasonable global calorie intake irrespective of the diet. OP rats showed higher food consumption and their calorie intake increased on HF. The mean abdominal fat % increase when on HF was higher in OP compared to CTRL and OR (236.1% vs. 89.97% and 65.99%). Total cholesterol and triglycerides were increased in OP-HF rats compared to the 5 other groups while OP showed a high nonHDL/HDL ratio already on SD. OP-HF rats had glucose intolerance. OP-HF rats showed an over time increase of systolic and diastolic arterial pressures and increased diastolic pressure at week 16 (117 ± 6 vs. 89 ± 6 and 93 ± 3 mmHg in OR-HF and CTRL-HF). Plasma leptin was increased in OP rats irrespective of the diet, suggesting a leptin resistance (4.8 ± 0.8 and 5.8 ± 0.5 ng/ml in OP-SD and OP-HF). In accordance with their satiety, leptin increased in CTRL and OR fed with HF (2.95 ± 0.6 and 2.98 ± 0.7 ng/ml vs. 0.65 ± 0.1 and 1 ± 0.1 ng/ml in CTRL-SD and OR-SD). The leptin/adiponectin ratio was elevated in OP regardless of the diet. The OP substrain is characterized by high plasma leptin and a loss of satiety leading to obesity and increased nonHDL/HDL ratio. When associated with HF, OP rats develop a metabolic syndrome.