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Summary 1. In the present study, we determined the effect of diet-induced obesity on cardiovascular and metabolic regulation in mice at standard laboratory temperatures (ambient temperature (T[sub a] ) = 22°C) and during exposure to thermoneutrality (T[sub a] = 30°C). 2. Male C57BL/6J (B6) mice fed a high-fat diet (HFF; n = 17) or chow (CHW; n = 14) for 15 weeks were surgically instrumented with telemetry devices, housed in metabolic chambers and assigned to either control or atenolol treatment (25 mg/kg per day in drinking water) to determine the effects of obesity on baseline cardiovascular function and on the responses to thermoneutrality and 24 h fasting. Mean arterial pressure (MAP), heart rate (HR), arterial pressure and HR variability (time and frequency domain), oxygen consumption (Vo[sub 2] ) and locomotor activity were determined. 3. The HFF mice exhibited increased bodyweight (+10.6 ± 4.1 g), moderate light period hypertension (+8.6 ± 2.6 mmHg), no difference in HR and increased HR variability at standard laboratory temperature compared with CHW controls. Atenolol produced less of a decrease in HR in HFF mice (-42 ± 10 b.p.m.) compared with CHW controls (-73 ± 15 b.p.m.). Acute exposure to thermoneutrality (T[sub a] = 30°C) reduced HR similarly in both HFF and CHW mice (approximately 175 b.p.m.), but reduced MAP less in HFF than in CHW mice (-7.3 ± 2.5 and -15.2 ± 1.0 mmHg), respectively. Atenolol treatment had only minor effects on the HR response to thermonuetrality (-114 ± 13 and -129 ± 8 b.p.m. in HFF and CHW mice, respectively). The HFF mice displayed greater fasting-induced reductions in light period MAP than did CHW mice (-10.0 ± 1.1 vs -3.1 ± 3.5 mmHg, respectively), whereas HR was decreased equally in both groups. Fasting-induced increases in HR variability were attenuated in HFF mice. 4. We conclude that diet-induced obesity produced generally minor changes in cardiovascular regulation in B6 mice at baseline, some of which are distinct from the effects of diet-induced obesity in larger animal models. In contrast, acute variations in T[sub a] or caloric availability produce pronounced alterations in cardiovascular function in either lean or obese mice, which are generally evident after atenolol and, thus, presumably not due exclusively to variation in cardiac sympathetic activity. Interestingly, the degree of obesity induced hypertension was augmented when mice were studied at thermonuetrality. The results suggest an important unrecognized role for vagal tone in the regulation of cardiovascular function in mice and support the need for considerable caution when using mouse models of obesity to examine regulation of cardiovascular function. We argue that mouse physiology studies should be performed in thermoneutral conditions. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]