Long non-coding RNA Bhmt-AS attenuates hepatic gluconeogenesis via modulation of Bhmt expression
Long non-coding RNA Bhmt-AS attenuates hepatic gluconeogenesis via modulation of Bhmt expression
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长链非编码 RNA Bhmt-AS 通过调节 Bhmt 表达来减弱肝脏糖异生
DOI：
10.1016/j.bbrc.2019.06.008
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发表时间：
2019-08-13
影响因子：
3.1
通讯作者：
Li, John Zhong
中科院分区：
文献类型：
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作者：
Shen, Xuan;Zhang, Yajun;Li, John Zhong
代谢产物生成的失调有助于代谢疾病的发病机制，例如2型糖尿病。长链非编码RNA（IncRNA）在糖尿病发病机制中的作用最近受到越来越多的关注。在本研究中，我们确定了一种新的IncRNA，甜菜碱同型半胱氨酸甲基转移酶反义（Bhmt-AS），并检查其在病理生理条件下的表达模式。我们的研究结果表明，Bhmt-AS的表达显着增加，在禁食和db/db小鼠的肝脏，并诱导致炎性激素刺激。Bhmt-AS也被证明是Bhmt表达的一致调节剂。在功能上，Bhmt-AS的耗竭抑制了体内和体外的肝葡萄糖产生。腺病毒介导的肝脏BhmtAS基因敲低可改善丙酮酸耐量、葡萄糖耐量和胰岛素敏感性。此外，在原代肝细胞中，Bhmt的过表达恢复了由Bhmt-AS敲低引起的葡萄糖产生减少。综上所述，我们发现了一种新的反义lncRNA（Bhmt-AS），它与Bhmt共表达，并在体外和体内一致地特异性调节Bhmt的表达，以调节肝脏的新生。(C)2019年，任作家。爱思唯尔公司出版这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Dysregulation of gluconeogenesis contributes to the pathogenesis of metabolic disease, such as type-2 diabetes. The role of long non-coding RNAs (IncRNAs) in the pathogenesis of diabetes has recently received increased attention. In the present study, we identified a novel IncRNA, betaine-homocysteine methyltransferase-antisense (Bhmt-AS), and examined its expression patterns under pathophysiological conditions. Our results revealed that the expression of Bhmt-AS was significantly increased in the livers of fasted and db/db mice and was induced by gluconeogenic hormonal stimuli. The Bhmt-AS was also shown to be a concordant regulator of Bhmt expression. Functionally, depletion of Bhmt-AS suppressed hepatic glucose production both in vivo and in vitro. Adenovirus-mediated hepatic knockdown of BhmtAS improved pyruvate tolerance, glucose tolerance, and insulin sensitivity. Furthermore, overexpression of Bhmt restored the decreased glucose production caused by knockdown of Bhmt-AS in primary hepatocytes. Taken together, we uncovered a novel antisense lncRNA (Bhmt-AS) that is co-expressed with Bhmt and concordantly and specifically regulates Bhmt expression both in vitro and in vivo to regulate hepatic gluconeogenesis. (C) 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).