Long non-coding RNA Bhmt-AS attenuates hepatic gluconeogenesis via modulation of Bhmt expression

作者：Xuan Shen, Yajun Zhang, Xu Zhang, Yiwei Yao, Yujie Zheng, Xianwei Cui, Chang Liu, Qian Wang, John Li · 发表于：Biochemical and Biophysical Research Communications · 年份：2019 · DOI：10.1016/j.bbrc.2019.06.008 · 被引用次数：16 · 研究领域：Cancer-related molecular mechanisms research、Lipid metabolism and disorders、RNA modifications and cancer

Dysregulation of gluconeogenesis contributes to the pathogenesis of metabolic disease, such as type-2 diabetes. The role of long non-coding RNAs (lncRNAs) in the pathogenesis of diabetes has recently received increased attention. In the present study, we identified a novel lncRNA, 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 Bhmt-AS 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.