RATIONALE Ambient temperature is a risk factor for cardiovascular disease. Cold weather increases cardiovascular events, but paradoxically, cold exposure is metabolically protective because of UCP1 (uncoupling protein 1)-dependent thermogenesis. OBJECTIVE We sought to determine the differential effects of ambient environmental temperature challenge and UCP1 activation in relation to cardiovascular disease progression. METHODS AND RESULTS Using mouse models of atherosclerosis housed at 3 different ambient temperatures, we observed that cold temperature enhanced, whereas thermoneutral housing temperature inhibited atherosclerotic plaque growth, as did deficiency in UCP1. However, whereas UCP1 deficiency promoted poor glucose tolerance, thermoneutral housing enhanced glucose tolerance, and this effect held even in the context of UCP1 deficiency. In conditions of thermoneutrality, but not UCP1 deficiency, circulating monocyte counts were reduced, likely accounting for fewer monocytes entering plaques. Reductions in circulating blood monocytes were also found in a large human cohort in correlation with environmental temperature. By contrast, reduced plaque growth in mice lacking UCP1 was linked to lower cholesterol. Through application of a positron emission tomographic tracer to track CCR2+ cell localization and intravital 2-photon imaging of bone marrow, we associated thermoneutrality with an increased monocyte retention in bone marrow. Pharmacological activation of β3-adrenergic receptors applied to mice housed at thermoneutrality induced UCP1 in beige fat pads but failed to promote monocyte egress from the marrow. CONCLUSIONS Warm ambient temperature is, like UCP1 deficiency, atheroprotective, but the mechanisms of action differ. Thermoneutrality associates with reduced monocyte egress from the bone marrow in a UCP1-dependent manner in mice and likewise may also suppress blood monocyte counts in man.

中文翻译：

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热中性而非UCP1缺乏抑制单核细胞动员进入血液。

理性环境温度是心血管疾病的危险因素。寒冷的天气会增加心血管事件，但自相矛盾的是，由于依赖UCP1（解偶联蛋白1）的生热作用，冷暴露在代谢上具有保护作用。目的我们试图确定周围环境温度挑战和UCP1激活与心血管疾病进展相关的不同影响。方法和结果使用在3种不同环境温度下容纳的动脉粥样硬化小鼠模型，我们观察到冷温度升高，而热中性住房温度则抑制了动脉粥样硬化斑块的生长，UCP1的缺乏也是如此。但是，尽管UCP1缺乏症会导致较差的葡萄糖耐量，但热中性住房会提高葡萄糖耐量，而且即使在UCP1缺乏症的情况下，这种影响也仍然存在。在热中性条件下，而非UCP1缺乏条件下，循环单核细胞计数减少，这可能解释了进入斑块的单核细胞减少。在与环境温度相关的大型人类队列中，还发现循环血单核细胞减少。相比之下，缺乏UCP1的小鼠斑块生长减少与胆固醇降低有关。通过应用正电子发射断层扫描示踪剂跟踪骨髓的CCR2 +细胞定位和活体2-光子成像，我们将热中性与骨髓中单核细胞保留增加相关联。β3-肾上腺素能受体的药理活化作用于热中性饲养的小鼠在米色脂肪垫中诱导了UCP1，但未能促进单核细胞从骨髓中流出。结论温暖的环境温度与UCP1缺陷一样，防动脉粥样硬化，但作用机制不同。热中性与UCP1依赖性小鼠单核细胞从骨髓流出的减少有关，同样也可能抑制人的血液单核细胞计数。