Cardiovascular, metabolic, and coronary dysfunction in high-Fat-Fed obesity-resistant/prone rats

Abstract

Objective Obesity is a global epidemic leading to several comorbidities including diabetes and cardiovascular disease. The hypothesis that the genetic background of the obesity-prone rat (OP) predisposes to physiologic, metabolic, and microvascular dysfunction which is exacerbated by a diet high in saturated fats was tested. Methods Male OP and obesity-resistant (OR) rats were fed either a diet containing 10% (chow) or 45% kcal fat (HF) for 42 weeks. Results Weight of OP rats was greater than OR rats by 8 weeks on both diets. Blood pressure was increased in OP rats on chow and further augmented by HF diet compared to OR rats on similar diets. In contrast to weight and blood pressure, glucose clearance was similar in OR and OP rats on chow and impaired in both models on HF diet. Relaxation to acetylcholine was attenuated in OP rats compared to OR rats by 8 weeks and remained reduced throughout the study. A longer period of time was required to observe vascular dysfunction in HF-fed OR rats. Conclusions When compared to OR rats, OP rats are prone to develop not only greater obesity but also hypertension and vascular dysfunction on a normal diet which is further augmented with HF diet.