van der Stelt Inge, Hoevenaars Femke, Široká Jitka, de Ronde Lidwien, Friedecký David, Keijer Jaap, van Schothorst Evert
Human and Animal Physiology, Wageningen University Wageningen, Netherlands.
Laboratory of Metabolomics, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc Olomouc, Czechia.
Front Physiol. 2017 Mar 23;8:179. doi: 10.3389/fphys.2017.00179. eCollection 2017.
Housing of laboratory mice at room temperature (22°C) might be considered a constant cold stress, which induces a thermogenic program in brown adipose tissue (BAT). However, the early adaptive response of white adipose tissue (WAT), the fat storage organ of the body, to a change from thermoneutrality to room temperature is not known. This was investigated here for various WAT depots, focusing on epididymal WAT (eWAT), widely used as reference depot. Male adult diet-induced obese (DIO) C57BL/6JOlaHsd mice housed at thermoneutrality (29°C), were for 5 days either switched to room temperature (22°C) or remained at thermoneutrality. Energy metabolism was continuously measured using indirect calorimetry. At the end of the study, serum metabolomics and WAT transcriptomics were performed. We confirmed activation of the thermogenic program in 22°C housed mice. Body weight and total fat mass were reduced. Whole body energy expenditure (EE) was increased, with a higher fatty acid to carbohydrate oxidation ratio and increased serum acylcarnitine levels, while energy intake was not significantly different between the two groups. Transcriptome analysis of eWAT identified tissue remodeling and inflammation as the most affected processes. Expression of pro-inflammatory M1 macrophage-related genes, and M1 over M2 macrophage ratio were decreased, which might be linked to an increased insulin sensitivity. Markers of thermogenesis were not altered in eWAT. Decreased expression of tryptophan hydroxylase 2 () and cholecystokinin () might represent altered neuroendocrine signaling. eWAT itself does not show increased fatty acid oxidation. The three measured WATs, epididymal, mesenteric, and retroperitoneal, showed mainly similar responses; reduced inflammation (s100a8), decreased carbohydrate oxidation, and no or small differences in fatty acid oxidation. However, Ucp1 was only expressed and increased in rWAT in 22°C housed mice. Cck expression was decreased in the three WATs, significantly in eWAT and rWAT, in contrast to Tph2, which was decreased in eWAT while not expressed in mWAT and rWAT. Our data show that tissue remodeling, inflammation and neuroendocrine signaling are early responses in WAT to a moderate decrease in environmental temperature.
将实验小鼠饲养在室温（22°C）下可能被视为一种持续的冷应激，这会在棕色脂肪组织（BAT）中诱导产热程序。然而，白色脂肪组织（WAT）作为身体的脂肪储存器官，对从热中性环境转变为室温的早期适应性反应尚不清楚。本研究针对不同的WAT储存部位进行了调查，重点关注广泛用作参考储存部位的附睾白色脂肪组织（eWAT）。将饲养在热中性环境（29°C）下的成年雄性饮食诱导肥胖（DIO）C57BL/6JOlaHsd小鼠，要么转移到室温（22°C）饲养5天，要么继续留在热中性环境中。使用间接量热法连续测量能量代谢。在研究结束时，进行了血清代谢组学和WAT转录组学分析。我们证实了饲养在22°C环境中的小鼠产热程序被激活。体重和总脂肪量减少。全身能量消耗（EE）增加，脂肪酸与碳水化合物氧化比更高，血清酰基肉碱水平升高，而两组之间的能量摄入没有显著差异。对eWAT的转录组分析确定组织重塑和炎症是受影响最大的过程。促炎M1巨噬细胞相关基因的表达以及M1与M2巨噬细胞的比例降低，这可能与胰岛素敏感性增加有关。eWAT中产热标志物未改变。色氨酸羟化酶2（）和胆囊收缩素（）的表达降低可能代表神经内分泌信号改变。eWAT本身并未显示脂肪酸氧化增加。所测量的三个WAT，附睾、肠系膜和腹膜后WAT，主要表现出相似的反应；炎症减轻（s100a8），碳水化合物氧化减少，脂肪酸氧化无差异或差异很小。然而，Ucp1仅在饲养在22°C环境中的小鼠的肾周白色脂肪组织（rWAT）中表达并增加。Cck在三个WAT中的表达均降低，在eWAT和rWAT中显著降低，而Tph2在eWAT中降低，在肠系膜白色脂肪组织（mWAT）和rWAT中未表达。我们的数据表明，组织重塑、炎症和神经内分泌信号是WAT对环境温度适度降低的早期反应。
