Retarded Learning in a Rabbit Model of Metabolic Syndrome Created by Long-Term Feeding of High-Fat Diet and High Sucrose.

Background: Metabolic syndrome is a constellation of medical conditions including central obesity, high blood sugar, and high triglycerides known to increase the risk of heart disease, stroke, and type 2 diabetes, with significant sex differences in the syndrome's incidence and prevalence. These clinical symptoms may be accompanied by cognitive impairment. Methods: In the present experiment, we fed rabbits a diet high in fat and sugar (HFSD), assessed symptoms, and measured changes in cognition using trace eyeblink conditioning. Results: We show that a range of symptoms of metabolic syndrome resulted from HFSD in male and female rabbits and obesity, high blood sugar, and glucose intolerance were higher in male than female rabbits. Specifically, HFSD male rabbits gained more weight and had a higher body-mass index, more body fat, higher fasting glucose levels, and greater glucose intolerance. Importantly, using trace and delay eyeblink conditioning, we show that there was cognitive impairment because of the high-fat and high-sugar diet in both male and female rabbits, but this was greater in HFSD male rabbits than HFSD female rabbits. Conclusions: Metabolic syndrome modeled in rabbits fed a diet high in fat and sugar reflects trends in the adult population including central obesity, high blood sugar, and high triglycerides and cognitive impairment and provides an important model and test bed for assessing interventions.