Induction of the metabolic regulator Txnip in fasting-induced and natural torpor.
Induction of the metabolic regulator Txnip in fasting-induced and natural torpor.
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DOI：
10.1210/en.2012-2051
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发表时间：
2013-06
期刊：
影响因子：
4.8
通讯作者：
Bechtold DA
中科院分区：
文献类型：
--
作者：
Hand LE;Saer BR;Hui ST;Jinnah HA;Steinlechner S;Loudon AS;Bechtold DA
麻痹是一种生理状态，其特征在于代谢率和核心体温的受控降低，从而在食物供应减少或恶劣环境条件下节省大量能量。下丘脑协调能量平衡和体温调节，并在指导麻木中发挥关键作用。我们最近发现，缺乏孤儿G蛋白偶联受体Gpr 50的小鼠很容易进入麻痹响应禁食，现在已经使用这些小鼠进行下丘脑基因表达的变化与麻痹状态的微阵列分析。这揭示了一个强大的诱导硫氧还蛋白相互作用蛋白（Txnip）在下丘脑的麻痹小鼠，这是证实了定量RT-PCR和蛋白质印迹分析。原位杂交鉴定的室管膜内衬的第三脑室的主要网站torpor-related表达Txnip。为了进一步表征Txnip和麻痹之间的关系，我们分析了Txnip在小鼠长期禁食、冷暴露和2-脱氧葡萄糖诱导的代谢低下以及西伯利亚仓鼠自然发生的麻痹发作中的表达。引人注目的是，明显上调Txnip的表达只观察到野生型小鼠时，驱动到麻木和在西伯利亚仓鼠的麻木。Txnip的增加不限于下丘脑，在白色脂肪组织、棕色脂肪组织和肝脏中也证实了过度表达。鉴于最近确定Txnip作为一种重要的分子营养传感器在调节能量代谢，我们的数据表明，Txnip表达升高是至关重要的，以调节能量消耗和燃料的使用，在极端的低代谢状态的麻木。
Torpor is a physiological state characterized by controlled lowering of metabolic rate and core body temperature, allowing substantial energy savings during periods of reduced food availability or harsh environmental conditions. The hypothalamus coordinates energy homeostasis and thermoregulation and plays a key role in directing torpor. We recently showed that mice lacking the orphan G protein-coupled receptor Gpr50 readily enter torpor in response to fasting and have now used these mice to conduct a microarray analysis of hypothalamic gene expression changes related to the torpor state. This revealed a strong induction of thioredoxin-interacting protein (Txnip) in the hypothalamus of torpid mice, which was confirmed by quantitative RT-PCR and Western blot analyses. In situ hybridization identified the ependyma lining the third ventricle as the principal site of torpor-related expression of Txnip. To characterize further the relationship between Txnip and torpor, we profiled Txnip expression in mice during prolonged fasting, cold exposure, and 2-deoxyglucose-induced hypometabolism, as well as in naturally occurring torpor bouts in the Siberian hamster. Strikingly, pronounced up-regulation of Txnip expression was only observed in wild-type mice when driven into torpor and during torpor in the Siberian hamster. Increase of Txnip was not limited to the hypothalamus, with exaggerated expression in white adipose tissue, brown adipose tissue, and liver also demonstrated in torpid mice. Given the recent identification of Txnip as a molecular nutrient sensor important in the regulation of energy metabolism, our data suggest that elevated Txnip expression is critical to regulating energy expenditure and fuel use during the extreme hypometabolic state of torpor.
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影响因子：
0.9
作者：
Mathew, T. C.
通讯作者：
Mathew, T. C.
影响因子：
7.8
作者：
Delavest, M.;Even, C.;Krebs, M-O
通讯作者：
Krebs, M-O
DOI：
10.1152/ajpregu.00310.2007
发表时间：
2007-11-01
影响因子：
2.8
作者：
Brown, Jason C. L.;Gerson, Alexander R.;Staples, James F.
通讯作者：
Staples, James F.
影响因子：
2.9
作者：
ATGIE, C;NIBBELINK, M;AMBID, L
通讯作者：
AMBID, L
影响因子：
--
作者：
NESTLER, JR
通讯作者：
NESTLER, JR