Naomi Berrie Diabetes Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Naomi Berrie Diabetes Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Mol Metab. 2023 Jul;73:101740. doi: 10.1016/j.molmet.2023.101740. Epub 2023 May 19.
Rodent models raised at environmental temperatures of 21-22 °C are increasingly switched to thermoneutral housing conditions in adulthood to better capture human physiology. We quantified the developmental effects of rearing mice at an ambient temperature of 22 °C vs. 30 °C on metabolic responses to cold and high fat diet (HFD) in adulthood.
Mice were reared from birth to 8 weeks of age at 22 °C or 30 °C, when they were acclimated to single housing at the same temperature for 2-3 weeks in indirect calorimetry cages. Energy expenditure attributable to basal metabolic rate, physical activity, thermic effect of food, and adaptive cold- or diet-induced thermogenesis was calculated. Responses to cooling were evaluated by decreasing the ambient temperature from 22 °C to 14 °C, while responses to HFD feeding were assessed at 30 °C. Influences of rearing temperature on thermogenic responses that emerge over hours, days and weeks were assessed by maintaining mice in the indirect calorimetry cages throughout the study.
At an ambient temperature of 22 °C, total energy expenditure (TEE) was 12-16% higher in mice reared at 22 °C as compared to 30 °C. Rearing temperature had no effect on responses in the first hours or week of the 14 °C challenge. Differences emerged in the third week, when TEE increased an additional 10% in mice reared at 22 °C, but mice reared at 30 °C could not sustain this level of cold-induced thermogenesis. Rearing temperature only affected responses to HFD during the first week, due to differences in the timing but not the strength of metabolic adaptations.
Rearing at 22 °C does not have a lasting effect on metabolic adaptations to HFD at thermoneutrality, but it programs an enhanced capacity to respond to chronic cold challenges in adulthood. These findings highlight the need to consider rearing temperature when using mice to model cold-induced thermogenesis.
在环境温度为 21-22°C 的情况下饲养的啮齿动物模型，在成年后越来越多地被转移到热中性环境中，以更好地模拟人类的生理状态。本研究旨在量化在环境温度为 22°C 和 30°C 下饲养小鼠对成年后冷刺激和高脂肪饮食（HFD）代谢反应的影响。
将小鼠从出生到 8 周龄分别饲养在 22°C 或 30°C 环境中，然后在 2-3 周的时间内适应相同温度的单笼饲养，在间接测热笼中测量基础代谢率、体力活动、食物的热效应以及适应性冷或饮食诱导产热的能量消耗。通过将环境温度从 22°C 降至 14°C 来评估对冷却的反应，同时在 30°C 下评估对 HFD 喂养的反应。通过在整个研究过程中让小鼠一直处于间接测热笼中，评估饲养温度对几小时、几天和几周内出现的产热反应的影响。
在环境温度为 22°C 时，22°C 组小鼠的总能量消耗（TEE）比 30°C 组高 12-16%。饲养温度对 14°C 挑战的前几个小时或一周内的反应没有影响。在第三周时，22°C 组的 TEE 增加了 10%，差异出现，但 30°C 组的小鼠无法维持这种水平的冷诱导产热。由于代谢适应的时机而不是强度的差异，饲养温度仅在第一周影响对 HFD 的反应。
在热中性条件下，22°C 饲养不会对 HFD 的代谢适应产生持久影响，但会在成年后对慢性冷刺激产生更强的适应能力。这些发现强调了在使用小鼠模拟冷诱导产热时需要考虑饲养温度的必要性。
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