Cardiovascular and metabolic regulation in mice with neuron specific deletion of the leptin receptor.

We showed that male leptin‐deficient mice do not develop hypertension despite severe metabolic abnormalities. We examined the impact of CNS leptin receptor (LR) deletion on energy balance and obesity‐induced elevations in blood pressure (BP) and heart rate (HR). BP and HR measured by telemetry, and motor activity (MA) and oxygen consumption (VO2) were monitored for 5 days in 24‐week‐old female and male LR/Nestin‐Cre (n=6/gender) and control mice (WT, n=5/gender). Female and male LR/Nestin‐Cre mice were heavier (60„b4 and 62±5 vs 24±1 g and 31±1 g) due to hyperphagia (5.2±0.5 and 6.2±0.5 vs 3.8±0.5 and 3.5±1.0 g/day) and reduced VO2 (30±2 and 27±1 vs 50±8 and 49±3 ml/kg/min) and MA (16±3 and 3±1 vs 507±80 and 676±105 cm/hr) compared to WT mice. LR/Nestin‐Cre mice were hyperleptinemic (109±2 vs 7±1 ng/ml) and hyperinsulinemic (119±23 vs 10±3 μU/ml), but had normal glucose levels (174±10 vs 180±11 mg/dl) compared to WT mice. Female LR/Nestin‐Cre mice exhibited higher BP than WT mice (117±2 vs 110±2 mmHg); BP in male LR/Nestin‐Cre was not different than in WT mice (110±1 vs 111±3 mmHg). HR was slightly lower in female and male LR/Nestin‐Cre mice (617±14 and 580±10) vs WT mice male and female mice (648±12 and 650¡Ó35 bpm). These results highlight the importance of CNS LRs in regulating appetite and energy expenditure and show potential gender differences in the impact of obesity on control of BP. (NHLBI‐PO1HL51971/AHA SDG5680016)