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

Xuan Shen; Yajun Zhang; Xu Zhang; Yiwei Yao; Yujie Zheng; Xianwei Cui; Chang Liu; Qian Wang; John Zhong Li

doi:10.1016/j.bbrc.2019.06.008

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

Biochem Biophys Res Commun. 2019 Aug 13;516(1):215-221. doi: 10.1016/j.bbrc.2019.06.008. Epub 2019 Jun 14.

Authors

Xuan Shen¹, Yajun Zhang¹, Xu Zhang¹, Yiwei Yao¹, Yujie Zheng¹, Xianwei Cui², Chang Liu³, Qian Wang⁴, John Zhong Li⁵

Affiliations

¹ The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; The Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
² Nanjing Maternity and Child Health Care Hospital, China; Women's Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210004, China.
³ School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China.
⁴ The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; The Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, 211166, China. Electronic address: wqian@njmu.edu.cn.
⁵ The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; The Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, 211166, China. Electronic address: lizhong@njmu.edu.cn.

PMID: 31208716
DOI: 10.1016/j.bbrc.2019.06.008

Abstract

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.

Keywords: Bhmt; Bhmt-AS; Hepatic gluconeogenesis; Long non-coding RNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Betaine-Homocysteine S-Methyltransferase / genetics*
Cells, Cultured
Gene Expression Regulation
Gene Knockdown Techniques
Gluconeogenesis*
Liver / metabolism*
Male
Mice
Mice, Inbred C57BL
RNA, Long Noncoding / genetics*
Up-Regulation

Substances

RNA, Long Noncoding
Betaine-Homocysteine S-Methyltransferase
Bhmt protein, mouse