Abstract
BackgroundSkeletal muscle is essential for glucose and lipid metabolism. Growing evidence reveals the importance of long non-coding RNAs (LncRNAs) in metabolism. This study aimed to investigate the function of LncRNA H19 (H19) in lipid metabolism of skeletal muscle and its potential mechanisms.MethodsGlucose tolerance, serum insulin and lipid content in serum and skeletal muscle were determined in control and H19-overexpressed db/db mice. Lipid metabolism was evaluated in H19-overexpressed or H19-silencing muscle cells by detecting lipid contents and mitochondria related functions. The underlying mechanisms were explored by RNA pull-down, mass spectrometry and RNA immunoprecipitation (RIP).ResultsH19 was downregulated in skeletal muscle of db/db mice. H19 overexpression in db/db mice inhibited lipid ectopic deposition in skeletal muscle, meanwhile improved glucose intolerance and insulin resistance as compared with control db/db mice treated with ad-GFP. Furthermore, overexpression of H19 reversed FFA-induced lipid accumulation and increased cellular respiration in muscle cells, while H19 knockdown exhibited opposite effects in muscle cells. Mechanistically, H19 interacted with heterogeneous nuclear ribonucleoprotein (hnRNPA1) which was validated by RNA pulldown and RIP analysis, which increased translation of fatty acid oxidation closely related genes PGC1a and CPT1b.ConclusionOur data suggest that overexpression of H19 ameliorates insulin resistance by reducing ectopic lipid accumulation in skeletal muscle. The possible underlying mechanisms are that overexpression of lncRNAH19 promotes fatty acids oxidation via targeting of hnRNPA1.3nDHbXWaWzN5EJ8oDSo3_JVideo abstract
Highlights
Skeletal muscle is essential for glucose and lipid metabolism
To test whether this could be recapitulated in the db/db mouse model, we examined H19 expression in skeletal muscle samples of db/db mice using RTqPCR
H19 overexpression in db/db mice was accomplished by tail vein injection of ad-H19 virus, followed by RT-qPCR to examine the effect of H19 overexpression in db/db mice
Summary
Skeletal muscle is essential for glucose and lipid metabolism. Growing evidence reveals the importance of long non-coding RNAs (LncRNAs) in metabolism. This study aimed to investigate the function of LncRNA H19 (H19) in lipid metabolism of skeletal muscle and its potential mechanisms. Several recent studies have revealed some new pathogenic mechanisms for IR and T2DM. Alicka et al [6] reported that impaired multipotency such as damaged proliferation, viability of ASCs which led to T2DM. In their findings, ASCs were a new promising therapeutic target for IR and T2DM. The pathogenesis of IR and T2DM is complex and multifaceted and need more studies to uncover
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