Chronic CNS-mediated cardiometabolic actions of leptin: potential role of sex differences.

Previous studies using male rodents showed the adipocyte-derived hormone leptin acts in the brain to regulate cardiovascular function, energy balance and glucose homeostasis. The importance of sex differences in cardiometabolic responses to leptin, however, is still unclear. We examined potential sex differences in leptin's chronic central nervous system (CNS)-mediated actions on blood pressure (BP), heart rate (HR), appetite, and glucose homeostasis in normal and type 1 diabetic rats. Female (n=6) and male (n=5) Sprague-Dawley rats were instrumented with intracerebroventricular (ICV) cannulas for continuous 7-day leptin infusion (15 mg/day) and BP and HR were measured by telemetry 24-hrs/day. At baseline, females had lower MAP (96±3 vs. 104±4 mmHg, p<0.05) but higher HR (375±5 vs. 335±5 bpm, p<0.05) compared to males. Following leptin treatment, we observed similar changes in BP (~3 mmHg) and HR (~25 bpm) in both sexes. Females had significantly reduced body weight (BW, 283±2 vs. 417±7 g, p<0.05) and lower caloric intake (162±20 vs. 192±9 kcal/kg of BW, p<0.05) compared to males, and leptin infusion reduced BW (-10%) and caloric intake (-62%) similarly in both sexes. Leptin infusion also caused similar reductions in fasting insulin and blood glucose levels in both sexes. In female and male rats with streptozotocin-induced diabetes (n=5/sex), ICV leptin treatment for 7 days completely normalized glucose levels. These results show that leptin's CNS effects on BP, HR, glucose regulation and energy homeostasis are similar in male and female rats. Therefore, our results provide no evidence for sex differences in leptin's brain-mediated cardiovascular or metabolic actions.