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Int J Biochem Cell Biol. 2018 Nov;104:14-24. doi: 10.1016/j.biocel.2018.08.013. Epub 2018 Sep 1.

Dynamic transcriptome profile in db/db skeletal muscle reveal critical roles for long noncoding RNA regulator.

Author information

1
The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, 210004, China; The First People's Hospital of Lianyungang, Xu Zhou Medical University Affiliated Hospital of LianYun Gang, The First Affiliated Hospital of KangDa College of Nanjing Medical University, LianYun Gang, 222000, China.
2
Department ofPediatrics, Jingjiang People's Hospital, Yangzhou University, Jingjiang, 214500, China.
3
Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
4
The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, 210004, China.
5
The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, 210004, China. Electronic address: y_lianghui@126.com.
6
The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, 210004, China. Electronic address: bluegn@163.com.
7
Department of Clinical Laboratory, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, 210004, China.

Abstract

T2DM is a global health problem that seriously lowers the quality of life and insulin resistance makes a considerable contribution to the pathophysiology of T2DM. Long noncoding RNAs (lncRNAs) have emerged as important regulators in glucose and lipid metabolism. However, comprehensive analysis of lncRNAs in db/db mice skeletal muscle and their potential roles involved in skeletal muscle insulin resistance (IR) remains poorly characterized. Here, we identified 331 lncRNAs, 172 upregulated and 159 downregulated (|fold change|>2, q<0.05), differentially expressed in db/db mice skeletal muscle. Gene Ontology analysis, Pathway analysis and Gene Set Enrichment Analysis of network gene expression revealed the potential functions of dysregulated lncRNAs may involve skeletal muscle function, fatty acid metabolism and the PPAR signaling pathway. In addition, differentially expressed lncRNAs were verified in skeletal muscle from the widely known IR mouse models (db/db and ob/ob mice). Further validation of lncRNAs in C2C12 myotubes exposed with various concentrations of palmitate uncovered that lncRNAs were responsive to palmitate exposure at the high concentrations (0.5mM and 0.75mM). Coexpression analysis revealed the key lncRNA-mRNA interactions and indicated a potential regulatory role of lncRNAs. Moreover, we characterized two candidate lncRNAs Gm15441 and 3110045C21Rik by a comprehensive examination of their genomic context and validated their expression with neighboring genes (Txnip and Ddr2) by the Spearman correlation analysis. Collectively, these findings improve our understanding of lncRNAs that mediate skeletal muscle insulin resistance in diabetes and represent potential molecular therapeutic targets to improve insulin sensitivity and associated metabolic diseases.

KEYWORDS:

Coexpression; Insulin resistance; Skeletal muscle; T2DM; lncRNA

PMID:
30179676
DOI:
10.1016/j.biocel.2018.08.013
[Indexed for MEDLINE]

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