Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
Am J Physiol Regul Integr Comp Physiol. 2012 Aug 15;303(4):R438-48. doi: 10.1152/ajpregu.00092.2012. Epub 2012 Jul 3.
We showed previously that, at ambient room temperature (22°C), mice maintained at 20% below their initial body weight by calorie restriction expend energy at a rate below that which can be accounted for by the decrease of fat and fat-free mass. Food-restricted rodents may become torpid at subthermoneutral temperatures, a possible confounding factor when using mice as human models in obesity research. We examined the bioenergetic, hormonal, and behavioral responses to maintenance of a 20% body weight reduction in singly housed C57BL/6J +/+ and Lep(ob) mice housed at both 22°C and 30°C. Weight-reduced high-fat-fed diet mice (HFD-WR) showed similar quantitative reductions in energy expenditure-adjusted for body mass and composition-at both 22°C and 30°C: -1.4 kcal/24 h and -1.6 kcal/24 h below predicted, respectively, and neither group entered torpor. In contrast, weight-reduced Lep(ob) mice (OB-WR) housed at 22°C became torpid in the late lights-off period (0200-0500) but did not when housed at 30°C. These studies indicate that mice with an intact leptin axis display similar decreases in "absolute" energy expenditure in response to weight reduction at both 22°C and 30°C ambient temperature. More importantly, the "percent" decrease in total energy expenditure observed in the HFD-WR compared with AL mice is much greater at 30°C (-19%) than at 22°C (-10%). Basal energy expenditure demands are ∼45% lower in mice housed at 30°C vs. 22°C, since the mice housed at thermoneutrality do not allocate extra energy for heat production. The higher total energy expenditure of mice housed at 22°C due to these increased thermogenic demands may mask physiologically relevant changes in energy expenditure showing that ambient temperature must be carefully considered when quantifying energy metabolism in both rodents and humans.
我们之前已经表明,在环境室温(22°C)下,通过热量限制将体重维持在初始体重的 20%以下的小鼠,其能量消耗率低于脂肪和去脂体重减少所解释的水平。在亚常温下,限制食物的啮齿动物可能会变得迟钝,这可能是在肥胖研究中将小鼠作为人类模型使用时的一个混杂因素。我们研究了单笼饲养的 C57BL/6J +/+ 和 Lep(ob)小鼠在 22°C 和 30°C 下维持 20%体重减轻时的生物能量、激素和行为反应。高脂肪喂养饮食减轻体重的小鼠(HFD-WR)在 22°C 和 30°C 下,能量消耗的定量减少相似,分别比预测值低-1.4 和-1.6 kcal/24 h,并且两组均未进入冬眠状态。相比之下,在 22°C 下饲养的减轻体重的 Lep(ob)小鼠在晚熄灯期(0200-0500)进入休眠状态,但在 30°C 下则没有。这些研究表明,具有完整瘦素轴的小鼠在 22°C 和 30°C 环境温度下对体重减轻的反应,其“绝对”能量消耗均会减少。更重要的是,与 AL 小鼠相比,HFD-WR 中观察到的总能量消耗的“百分比”减少在 30°C(-19%)时比在 22°C(-10%)时更大。由于在 30°C 下饲养的小鼠的基础能量消耗需求约为 22°C 的 45%,因为在热中性下饲养的小鼠不会为产热分配额外的能量。由于这些增加的产热需求,在 22°C 下饲养的小鼠的总能量消耗更高,这可能掩盖了能量消耗方面的生理相关变化,表明在定量分析啮齿动物和人类的能量代谢时,环境温度必须得到仔细考虑。