Metabolic and Coronary Dysfunction in Obesity Resistant and Obesity Prone High Fat Fed Rats

Abstract

The purpose of this study was to compare physiologic, metabolic and microvascular complications in obesity resistant (OR) and obesity prone (OP) rats fed a high fat (HF) diet. 8 week old male rats were fed a diet containing 45% kcal saturated fat for 42 weeks. Blood pressure was measured by telemetry. Reactivity of small (75 – 150 μm intraluminal diameter) coronary arteries was evaluated. Body weights were 504±7, 669±25*, 685±8*, and 924±39* grams for OR control, OR HF, OP control OP HF rats, respectively. Blood pressure was increased in OP rats on control diet (121.5 ± 4.3mmHg*) and further increased with HF diet (129.7 ± 2.4mmHg*), compared to OR rats on control (98.3 ± 4.3mmHg) or HF diet (99.5 ± 3.1mmHg). Glucose clearance was impaired in high fat fed OR and OP rats. Acetylcholine (ACh)‐mediated relaxation of coronary arteries from HF fed rats was impaired (% relaxation to 10 μM Ach: OR control=67 ± 10, OR HF = 36±12*, OP control = 41±8*, and OP HF = 22±6*). Sodium nitroprusside (SNP) responses were not altered (% relaxation to 0.1 mM SNP: OR control = 72 ± 5, OR HF = 60 ± 7, OP control = 62 ± 8, and OP HF = 74 ± 6%). *p<0.05 vs OR control diet. These studies indicate that HF diet augments metabolic and microvascular complications in OP rats.Supported by VA Merit to Dr. Oltman.