Cardiovascular and metabolic responses to chronic central infusion of leptin in rats fed a high fat diet

Abstract

Obesity has been reported to be associated with "resistance" to the metabolic effects of leptin. However, previous studies have tested only acute responses to leptin. The purpose of the current study was to test the hypothesis that a high fat (HF) diet causes resistance to the appetite and cardiovascular responses to chronic central leptin infusion. Sprague Dawley (SD) rats were fed a HF diet (40% kcal from fat, n=6) or a normal fat diet (NF, 13% kcal from fat, n=5) for 1 year starting at 3 weeks of age. Radiotelemeters were implanted for continuous monitoring of blood pressure (BP) and heart rate (HR). A 21G cannula was placed into the lateral cerebral ventricle (ICV). After recovery and 5 days of control measurements, leptin was infused ICV at 0.02 μg/kg/min for 10 days. Body weight in HF rats was 14% heavier than NF rats (581±17 vs. 510±17 g) and was associated with significantly higher BP (118±2 vs. 96±1 mmHg). Chronic ICV infusion of leptin decreased caloric intake in HF and NF rats similarly (51 ± 4% vs. 42 ± 1%) by day 5, remaining decreased throughout infusion. Despite decreased food intake and weight loss, BP and HR increased during the last 4 days of leptin infusion in both HF and NF rats (5.4 ± 0.6 vs. 5.0 ± 0.5 mmHg and 17 ± 3 vs. 17 ± 2 bpm). These results suggest this model of dietary‐induced obesity does not develop resistance to the chronic effects of central leptin administration on appetite or BP and HR regulation. (NHLBI PO1 HL51971).