Cardiovascular and metabolic responses to fasting and thermoneutrality in Ay mice

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Physiology and Behavior


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-Ay) mice would exhibit blunted physiologic responses to fasting and thermoneutrality. Male B6.Cg-Ay mice (Ay; 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 (Ta=23°C) to determine the effects of a 24-h fasting and exposure to thermoneutrality (Ta=30°C) on mean arterial pressure (MAP), heart rate (HR), AP and HR variability (time and frequency domain), oxygen consumption (VO2), and locomotor activity. Ay mice exhibited elevated baseline light-period MAP (Ay: 113±4; B6: 99±3 mm Hg) and VO2 (Ay: 1.82±0.08 vs. B6: 1.45±0.13 ml/min) with no difference in HR (Ay: 530±12 vs. B6: 548±19 bpm). At 12-24 h after food removal, Ay mice displayed normal fasting-induced bradycardia (Ay: -106±12; B6: -117±19 bpm) and reduction in VO2 (Ay: -0.19±0.04 vs. B6: -0.28±0.05 ml/min), but with augmented hypotension (Ay: -9±2 vs. B6: -0.5±2 mm Hg) and blunted hyperactivity (Ay: 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 Ay 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. © 2003 Elsevier Science Inc. All rights reserved.

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