Adaptive thermogenesis and thermal conductance in wild-type and UCP1-KO mice
Adaptive thermogenesis and thermal conductance in wild-type and UCP1-KO mice
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DOI：
10.1152/ajpregu.00021.2009
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发表时间：
2010-11-01
影响因子：
2.8
通讯作者：
Klingenspor, Martin
中科院分区：
文献类型：
--
作者：
Meyer, Carola W.;Willershaeuser, Monja;Klingenspor, Martin
Meyer CW，Willershauser M，Jstroch M，Rourke BC，Fromme T，Oelkrug R，Heldmaier G，Klingenspor M.野生型和UCP1-KO小鼠的适应性产热和热导。Am J Physiol Regul Integr Comp Physiol 299：R1396-R1406,2010.2010年9月8日首次出版；DOI：10.1152/ajpregu.00021.2009。-我们比较了温暖(WA；27摄氏度)、中度寒冷(Mca；18摄氏度)或寒冷驯化(CA；5摄氏度)野生型和解偶联蛋白1基因敲除(UCP1-KO)小鼠的最大冷诱导热产生(HPmax)和冷极限。在野生型小鼠中，MCA和CA后HPmax依次升高，冷限分别降至-8.3℃和-18.0℃。UCP1-KO小鼠对MCA和CA的反应也使HPmax增加，尽管幅度较小。直接比较显示，在野生型和UCP1-KO小鼠中，冷诱导的产热增加最大值分别为+473 mW和+227 mW。UCP1-KO小鼠的耐寒力从MCA的-0.9摄氏度增加到CA的-10.1摄氏度，与HPmax的变化没有直接关系，这表明UCP1-KO小鼠比野生型小鼠更有效地利用散热。从呼吸商判断，急性寒冷挑战UCP1-KO小鼠表现出向脂质氧化的延迟转变，5h的冷暴露显示体力活动减少，代谢率控制方面的变异性较小。我们的结论是，BAT是最大限度的适应性产热所必需的，但也允许代谢的灵活性，并作为对寒冷的急性反应，迅速转向持续的脂类燃料供热。在两个CA组中，收缩蛋白(肌球蛋白重链亚型)的表达在骨骼肌中表现出轻微的训练效应，而UCP1-KO小鼠的心肌中有新的β心脏亚型的表达。骨骼肌线粒体的呼吸作用和基础质子电导在不同基因型间均无差异。在UCP1-KO小鼠的皮下白色脂肪组织中，冷暴露使细胞色素-c氧化酶活性和细胞死亡诱导的DFFA样效应物A的表达分别增加3.6倍和15倍，表明富含线粒体的棕色脂肪细胞样细胞的招募。缺乏功能性BAT会导致白色脂肪组织的重塑，这可能对冷习服过程中的适应性产热有重要贡献。
Meyer CW, Willershauser M, Jastroch M, Rourke BC, Fromme T, Oelkrug R, Heldmaier G, Klingenspor M. Adaptive thermogenesis and thermal conductance in wild-type and UCP1-KO mice. Am J Physiol Regul Integr Comp Physiol 299: R1396-R1406, 2010. First published September 8, 2010; doi:10.1152/ajpregu.00021.2009.-We compared maximal cold-induced heat production (HPmax) and cold limits between warm (WA; 27 degrees C), moderate cold (MCA; 18 degrees C), or cold acclimated (CA; 5 degrees C) wild-type and uncoupling-protein 1 knockout (UCP1-KO) mice. In wild-type mice, HPmax was successively increased after MCA and CA, and the cold limit was lowered to -8.3 degrees C and -18.0 degrees C, respectively. UCP1-KO mice also increased HPmax in response to MCA and CA, although to a lesser extent. Direct comparison revealed a maximal cold-induced recruitment of heat production by +473 mW and +227 mW in wild-type and UCP1-KO mice, respectively. The increase in cold tolerance of UCP1-KO mice from -0.9 degrees C in MCA to -10.1 degrees C in CA could not be directly related to changes in HPmax, indicating that UCP1-KO mice used the dissipated heat more efficiently than wild-type mice. As judged from respiratory quotients, acutely cold-challenged UCP1-KO mice showed a delayed transition toward lipid oxidation, and 5-h cold exposure revealed diminished physical activity and less variability in the control of metabolic rate. We conclude that BAT is required for maximal adaptive thermogenesis but also allows metabolic flexibility and a rapid switch toward sustained lipid-fuelled thermogenesis as an acute response to cold. In both CA groups, expression of contractile proteins (myosin heavy-chain isoforms) showed minor training effects in skeletal muscles, while cardiac muscle of UCP1-KO mice had novel expression of beta cardiac isoform. Neither respiration nor basal proton conductance of skeletal muscle mitochondria were different between genotypes. In subcutaneous white adipose tissue of UCP1-KO mice, cold exposure increased cytochrome-c oxidase activity and expression of the cell death-inducing DFFA-like effector A by 3.6-fold and 15-fold, respectively, indicating the recruitment of mitochondria-rich brown adipocyte-like cells. Absence of functional BAT leads to remodeling of white adipose tissue, which may significantly contribute to adaptive thermogenesis during cold acclimation.