Abstract
Insulin resistance (IR) has been considered as the common pathological basis and developmental driving force for most metabolic diseases. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators in modulation of glucose and lipid metabolism. However, the comprehensive profile of lncRNAs in skeletal muscle cells under the insulin resistant status and the possible biological effects of them were not fully studied. In this research, using C2C12 myotubes as cell models in vitro, deep RNA-sequencing was performed to profile lncRNAs and mRNAs between palmitic acid-induced IR C2C12 myotubes and control ones. The results revealed that a total of 144 lncRNAs including 70 up-regulated and 74 down-regulated (|fold change| > 2, q < 0.05) were significantly differentially expressed in palmitic acid-induced insulin resistant cells. In addition, functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases revealed that the target genes of the differentially expressed lncRNAs were significantly enriched in fatty acid oxidation, lipid oxidation, PPAR signaling pathway, and insulin signaling pathway. Moreover, Via qPCR, most of selected lncRNAs in myotubes and db/db mice skeletal muscle showed the consistent expression trends with RNA-sequencing. Co-expression analysis also explicated the key lncRNA–mRNA interactions and pointed out a potential regulatory network of candidate lncRNA ENSMUST00000160839. In conclusion, the present study extended the skeletal muscle lncRNA database and provided novel potential regulators for future genetic and molecular studies on insulin resistance, which is helpful for prevention and treatment of the related metabolic diseases.
Highlights
Insulin resistance (IR) is considered as the common pathological basis and progressive driving force for several metabolic diseases, including obesity, Type 2 diabetes mellitus (T2DM), hyperlipidemia, hypertension, and coronary heart disease [1,2,3]
A detailed characterization of long noncoding RNA (lncRNA) on skeletal muscle glucose and lipid metabolism is essential for identifying new regulators and their proposed relevance related to insulin resistance (IR) pathophysiology and prevention
One study identified that more than 150 lncRNAs were dysregulated in the skeletal muscles from insulin-treated mice, which were related to glucose and lipid utilization [42]
Summary
Insulin resistance (IR) is considered as the common pathological basis and progressive driving force for several metabolic diseases, including obesity, Type 2 diabetes mellitus (T2DM), hyperlipidemia, hypertension, and coronary heart disease [1,2,3]. To maintain whole-body metabolic homeostasis, intensive interest has been focused on exploring the molecular mechanisms underlying the development of IR. The main feature of IR is impaired of physiological responses to normal insulin concentrations in peripheral target tissues including muscle, liver and adipose tissues. IR is characterized by the defective of insulin sensitivity in related tissues, which leads to a disturbance in glucose and lipid metabolism. Skeletal muscle, accounting for about 40% of the body mass, is both a locomotive organ and an important organ for 80% of the body’s glucose uptake, which is used to maintain metabolic balance [4,5,6]. Evidence has confirmed the importance of skeletal muscle responsible for modulating peripheral insulin
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