Cardiovascular and metabolic responses to fasting and thermoneutrality in A^y mice

Several lines of evidence support a role for reduced melanocortin signaling in the regulation of metabolic rate and cardiovascular function during negative energy balance. We tested the hypothesis that agouti yellow (B6.Cg-A^y) mice would exhibit blunted physiologic responses to fasting and thermoneutrality. Male B6.Cg-A^y mice (A^y; n=11, 34±2 g) and lean B6 littermates (B6; n=7, 26±2 g) were implanted with telemetry devices and housed in metabolic chambers (T_a=23°C) to determine the effects of a 24-h fasting and exposure to thermoneutrality (T_a=30°C) on mean arterial pressure (MAP), heart rate (HR), AP and HR variability (time and frequency domain), oxygen consumption (VO₂), and locomotor activity. A^y mice exhibited elevated baseline light-period MAP (A^y: 113±4; B6: 99±3 mm Hg) and VO₂ (A^y: 1.82±0.08 vs. B6: 1.45±0.13 ml/min) with no difference in HR (A^y: 530±12 vs. B6: 548±19 bpm). At 12-24 h after food removal, A^y mice displayed normal fasting-induced bradycardia (A^y: -106±12; B6: -117±19 bpm) and reduction in VO₂ (A^y: -0.19±0.04 vs. B6: -0.28±0.05 ml/min), but with augmented hypotension (A^y: -9±2 vs. B6: -0.5±2 mm Hg) and blunted hyperactivity (A^y: 27±23 vs. B6: 122±42 m/11 h). Fasting was associated with increased HR variability in both time and frequency domain in B6 but not A^y mice. Exposure to thermoneutrality produced comparable reductions in MAP, HR, and VO₂ in both strains. We conclude that inhibition of melanocortin signaling is not requisite for, but participates in, the metabolic and cardiovascular responses to negative energy balance.