Prolonged High-Fat Diet Feeding of WHHLMI Rabbits does Not Aggravate Metabolic or Cardiac Dysfunction

Myocardial infarction (MI)-prone Watanabe hereditary hyperlipidemic (WHHLMI) rabbits were reported to spontaneously but slowly develop MI, associated with enhanced coronary atherosclerosis and metabolic syndrome features. Our aim was to accelerate these processes by exposing the rabbits to a high-fat diet (HFD) that was previously shown to induce insulin resistance and cardiac injury in rabbits. HFD feeding for one year was indeed associated with development of obesity (37% increases in body weight, as compared to 3.7% for control standard-fat diet, SFD). On HFD, liver weight and hepatic triglyceride content were significantly higher as compared to SFD, with mild steatosis. Glucose and insulin levels were not markedly different on SFD or HFD, however after 1 year of diet treatment, HFD-fed animals were more glucose intolerant as compared to SFD-fed rabbits. On SFD, the rabbits developed marked thoracic aorta stenosis and calcification of atherosclerotic lesions, which were not aggravated by HFD feeding. Cardiac function analysis by MRI and transthoracic echocardiography did not reveal significant differences between SFD and HFD fed rabbits. Thus, the metabolic and cardiac phenotype of WHHLMI rabbits was not aggravated by HFD feeding for one year, and the rabbits did not spontaneously develop diabetes or myocardial infarction.