Altered microRNA expression in skeletal muscle results from high-fat diet-induced insulin resistance in mice

Abstract

Abstract. Skeletal muscle insulin resistance induced by a high-fat diet has been implicated in the development of type 2 diabetes. However, the precise molecular mechanisms involved are only partially understood. Recently, studies have shown that microRNAs play an important role in insulin resistance in various tissues. In this study, microRNA expression profiles of skeletal muscle of mice fed a high-fat or normal diet were analyzed using microarrays and the results were confirmed by real-time reverse-transcription polymerase chain reaction. Gene Ontology (GO) and pathway mapping tools were employed to analyze systemically the biological processes and signaling pathways affected by the differential expression of microRNAs. In this study, we show that 30 microRNAs are differentially expressed between 2 groups of mice. Compared to the mice fed a normal diet, there were 8 microRNAs up-regulated and 22 microRNAs down-regulated in the highfat diet-fed mice. Furthermore, we confirm that the MAPK signaling pathway highlighted in this study is involved in skeletal muscle insulin resistance. These results indicate that skeletal muscle insulin resistance induced by a high-fat diet is associated with a group of microRNAs. GO and pathway mapping are a valid and effective approach for analyzing the function of microRNAs and the results could be a guideline for further investigation.

microManaging glucose and lipid metabolism in skeletal muscle: Role of microRNAs

“…In skeletal muscle from T2D patients, miR-133a and miR-206 were downregulated as compared to normal glucose tolerant people and this reduction was correlated with fasting glucose values [12], although the reduction in miR-133a was not observed in a separate cohort [24]. Downregulation of miR-206 and miR-133 has also been reported in skeletal muscle of mice following 12 weeks of high fat diet [18,19]. In human skeletal muscle, miR-206 was also reduced after 10 days of bed rest [25].…”

“…As the studies used not only different microarray technologies, but also different analysis methods, direct comparison is challenging. More importantly, only few studies specifically report the actual skeletal muscle type investigated, for example, soleus [16] and gastrocnemius [18,19], with other studies omitting to describe which skeletal muscle was chosen (Table 1) [14,15,17].…”

“…In rodent models of obesity and diabetes, miRNA expression profiles have been determined in skeletal muscle of Goto-Kakizaki (GK) rats, a non-obese spontaneous T2D rat model [14][15][16], rats rendered diabetic by combination of high fat diet fed and low dose of streptozotocin (HFD/STZ) [17], as well as high fat diet fed mice (HFD) [18,19]. The differentially expressed miRNAs found to be dysregulated in skeletal muscle of these diabetic animal models are listed in table 1.…”

“…↑ miR-106b ↑ HFD mouse [18] Glut4 translocation; Mnf2 (mitochondrial fusion) [61] ↑ miR-143 ↑ HFD mouse [18] HK2 -Glycolysis (Cancer cells) [ …”

A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus

“…However, many other factors, both endogenous and exogenous, may influence the spectrum of miRNA in tissues and circulation. Recent findings suggest that diet, a key component in T2DM disease management, affects the spectra of miRNA in various tissues [109,110]. For example, the consumption of milk resulted in significant increases of miRNA levels in plasma and PBMCs [111].…”