MicroRNA-223 Expression Is Upregulated in Insulin Resistant Human Adipose Tissue

Abstract

MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression and influence many cellular functions including glucose and lipid metabolism. We previously reported that adipose tissue (AT) from women with polycystic ovary syndrome (PCOS) or controls with insulin resistance (IR) revealed a differentially expressed microRNA (miRNA) profile, including upregulated miR-93 in PCOS patients and in non-PCOS women with IR. Overexpressed miR-93 directly inhibited glucose transporter isoform 4 (GLUT4) expression, thereby influencing glucose metabolism. We have now studied the role of miR-223, which is also abnormally expressed in the AT of IR subjects. Our data indicates that miR-223 is significantly overexpressed in the AT of IR women, regardless of whether they had PCOS or not. miR-223 expression in AT was positively correlated with HOMA-IR. Unlike what is reported in cardiomyocytes, overexpression of miR-223 in human differentiated adipocytes was associated with a reduction in GLUT4 protein content and insulin-stimulated glucose uptake. In addition, our data suggests miR-223 regulates GLUT4 expression by direct binding to its 3′ untranslated region (3′UTR). In conclusion, in AT miR-223 is an IR-related miRNA that may serve as a potential therapeutic target for the treatment of IR-related disorders.

MicroRNAs-Mediated Regulation of Skeletal Muscle GLUT4 Expression and Translocation in Insulin Resistance

“…Another miRNA confirmed as a direct regulator of Slc2a4 /GLUT4 is the miR-223-3p, which has been described as upregulated in adipose tissue of women with insulin resistance [112]. In fact, overexpression of miR-223-3p in human adipocytes was reported to inhibit insulin-stimulated glucose uptake and to decrease GLUT4 protein content [112].…”

Regulatory Roles of MicroRNAs in Diabetes

“…As the last step in the insulin signaling pathway, GLUT4-mediated glucose uptake plays a crucial role in maintaining glucose homeostasis. GLUT4 can be directly inhibited by miR-199a and miR-93/223 in skeletal muscle and adipose tissue, respectively, which consequently has a negative impact on insulin sensitivity [52,53,54]. …”

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

“…Upregulation of miR-223 was reported in skeletal muscle of rats rendered diabetic by combination of high fat diet and low dose of streptozotocin [17], as well as in heart and adipose tissue from insulin resistant humans [30,31]. While overexpression of miR-223 increased insulin-stimulated glucose uptake and induced GLUT4 expression in cardiomyocytes, the opposite effects have been found in adipocytes, where miR-223 negatively regulates glucose uptake and GLUT4 protein abundance [30,31].…”

“…While overexpression of miR-223 increased insulin-stimulated glucose uptake and induced GLUT4 expression in cardiomyocytes, the opposite effects have been found in adipocytes, where miR-223 negatively regulates glucose uptake and GLUT4 protein abundance [30,31]. So far, the precise role of miR-223 in skeletal muscle remains unknown.…”