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Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1607-12. doi: 10.1073/pnas.1421419112. Epub 2015 Jan 20.

Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation.

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Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, and.
Department of Cellular and Molecular Physiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510;
Department of Cellular and Molecular Physiology.
Department of Biology, University of Wisconsin, Oshkosh, WI 54901; and.
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
Department of Cellular and Molecular Physiology,
Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, and


Hibernating mammals possess a unique ability to reduce their body temperature to ambient levels, which can be as low as -2.9 °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.


UCP1; hibernation; thermogenesis; thirteen-lined ground squirrel; uncoupling protein

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