Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

被引:39
作者
Laursen, Willem J. [1 ,2 ]
Mastrotto, Marco [1 ,2 ]
Pesta, Dominik [1 ,3 ]
Funk, Owen H. [1 ]
Goodman, Jena B. [1 ,2 ]
Merriman, Dana K. [4 ]
Ingolia, Nicholas [5 ]
Shulman, Gerald I. [1 ,3 ]
Bagriantsev, Sviatoslav N. [1 ]
Gracheva, Elena O. [1 ,2 ]
机构
[1] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA
[2] Yale Univ, Sch Med, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT 06510 USA
[3] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA
[4] Univ Wisconsin, Dept Biol, Oshkosh, WI 54901 USA
[5] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
基金
美国国家卫生研究院;
关键词
thirteen-lined ground squirrel; uncoupling protein; hibernation; thermogenesis; UCP1; BROWN-ADIPOSE-TISSUE; MAMMALIAN NONSHIVERING THERMOGENESIS; MITOCHONDRIAL UNCOUPLING PROTEIN-1; GROUND-SQUIRRELS; SKELETAL-MUSCLE; EVOLUTIONARY HISTORY; PURINE NUCLEOTIDES; FAT MITOCHONDRIA; GENE-EXPRESSION; LOW-TEMPERATURE;
D O I
10.1073/pnas.1421419112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hibernating mammals possess a unique ability to reduce their body temperature to ambient levels, which can be as low as -2.9 degrees C, by active down-regulation of metabolism. Despite such a depressed physiologic phenotype, hibernators still maintain activity in their nervous systems, as evidenced by their continued sensitivity to auditory, tactile, and thermal stimulation. The molecular mechanisms that underlie this adaptation remain unknown. We report, using differential transcriptomics alongside immunohistologic and biochemical analyses, that neurons from thirteen-lined ground squirrels (Ictidomys tridecemlineatus) express mitochondrial uncoupling protein 1 (UCP1). The expression changes seasonally, with higher expression during hibernation compared with the summer active state. Functional and pharmacologic analyses show that squirrel UCP1 acts as the typical thermogenic protein in vitro. Accordingly, we found that mitochondria isolated from torpid squirrel brain show a high level of palmitate-induced uncoupling. Furthermore, torpid squirrels during the hibernation season keep their brain temperature significantly elevated above ambient temperature and that of the rest of the body, including brown adipose tissue. Together, our findings suggest that UCP1 contributes to local thermogenesis in the squirrel brain, and thus supports nervous tissue function at low body temperature during hibernation.
引用
收藏
页码:1607 / 1612
页数:6
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