Ketogenic diet induces expression of the muscle circadian gene Slc25a25 via neural pathway that might be involved in muscle thermogenesis.
Ketogenic diet induces expression of the muscle circadian gene Slc25a25 via neural pathway that might be involved in muscle thermogenesis.
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DOI：
10.1038/s41598-017-03119-8
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发表时间：
2017-06-06
影响因子：
4.6
通讯作者：
Oishi K
中科院分区：
文献类型：
--
作者：
Nakao R;Shimba S;Oishi K
我们最近发现，Slc25a25的mRNA表达，钙敏感的ATP载体在线粒体内膜，在小鼠骨骼肌中的昼夜节律的方式波动。我们在这里表明，肌肉Slc25a25的昼夜节律表达在Clock突变，肌肉特异性Bmal1缺陷和全球Bmal1缺陷小鼠中受到抑制。此外，生酮饮食（KD），诱导一天中的时间依赖性低温（麻木），诱导骨骼肌中的Slc25a25 mRNA的表达。KD诱导的低温不影响肌肉中的Sarcolipin和Pgc1a以及脂肪组织中的Ucp1等产热基因。坐骨神经切断废除昼夜节律和KD诱导的Slc25a25表达，表明昼夜节律钟通过神经通路调节肌肉Slc25a25表达。我们测量体温（Tb）在坐骨神经失神经小鼠饲养KD，以确定KD诱导的Slc25a25表达的功能作用。坐骨神经切除废除Slc25a25的表达和增强KD诱导的低温与假手术小鼠相比，但不影响Tb在小鼠给予正常饮食。这些结果表明，KD喂养诱导肌肉昼夜节律基因Slc25a25通过神经通路的表达，SLC25A25可能参与肌肉产热KD诱导的低温下哺乳动物。
We recently found that the mRNA expression of Slc25a25, a Ca2+-sensitive ATP carrier in the inner mitochondrial membrane, fluctuates in a circadian manner in mouse skeletal muscle. We showed here that the circadian expression of muscle Slc25a25 was damped in Clock mutant, muscle-specific Bmal1-deficient, and global Bmal1-deficient mice. Furthermore, a ketogenic diet (KD) that induces time-of-day-dependent hypothermia (torpor), induced Slc25a25 mRNA expression in skeletal muscle. Hypothermia induced by KD did not affect thermogenic genes such as Sarcolipin and Pgc1a in muscles and Ucp1 in adipose tissues. Sciatic denervation abolished circadian and KD-induced Slc25a25 expression, suggesting that the circadian clock regulates muscle Slc25a25 expression via neural pathways. We measured body temperature (Tb) in sciatic denervated mice fed with KD to determine the functional role of KD-induced Slc25a25 expression. Sciatic denervation abolished Slc25a25 expression and augmented KD-induced hypothermia compared with sham-operated mice, but did not affect Tb in mice given a normal diet. These findings suggest that KD feeding induces expression of the muscle circadian gene Slc25a25 via neural pathways, and that SLC25A25 might be involved in muscle thermogenesis under KD-induced hypothermia in mammals.