title: Integrative mRNA-microRNA analyses reveal novel interactions related to insulin sensitivity in human adipose tissue.
abstract: Adipose tissue has profound effects on whole-body insulin sensitivity. However, the underlying biological processes are quite complex and likely multifactorial. For instance, the adipose transcriptome is posttranscriptionally modulated by microRNAs, but the relationship between microRNAs and insulin sensitivity in humans remains to be determined. To this end, we utilized an integrative mRNA-microRNA microarray approach to identify putative molecular interactions that regulate the transcriptome in subcutaneous adipose tissue of insulin-sensitive (IS) and insulin-resistant (IR) individuals. Using the NanoString nCounter Human v1 microRNA Expression Assay, we show that 17 microRNAs are differentially expressed in IR vs. IS. Of these, 16 microRNAs (94%) are downregulated in IR vs. IS, including miR-26b, miR-30b, and miR-145. Using Agilent Human Whole Genome arrays, we identified genes that were predicted targets of miR-26b, miR-30b, and miR-145 and were upregulated in IR subjects. This analysis produced ADAM22, MYO5A, LOX, and GM2A as predicted gene targets of these microRNAs. We then validated that miR-145 and miR-30b regulate these mRNAs in differentiated human adipose stem cells. We suggest that use of bioinformatic integration of mRNA and microRNA arrays yields verifiable mRNA-microRNA pairs that are associated with insulin resistance and can be validated in vitro.
authors.affiliation: College of Health Sciences, University of Kentucky, Lexington, Kentucky;
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Kirby
authors.affiliation: College of Health Sciences, University of Kentucky, Lexington, Kentucky;
authors.forename: R Grace
authors.initials: RG
authors.lastname: Walton
authors.affiliation: Department of Medicine, Division of Endocrinology, and Barnstable Brown Diabetes and Obesity Center; University of Kentucky, Lexington, Kentucky; and.
authors.forename: Brian
authors.initials: B
authors.lastname: Finlin
authors.affiliation: Department of Medicine, Division of Endocrinology, and Barnstable Brown Diabetes and Obesity Center; University of Kentucky, Lexington, Kentucky; and.
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Medicine, Division of Endocrinology, and Barnstable Brown Diabetes and Obesity Center; University of Kentucky, Lexington, Kentucky; and.
authors.forename: Resat
authors.initials: R
authors.lastname: Unal
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, University of Colorado, Aurora, Colorado.
authors.forename: Neda
authors.initials: N
authors.lastname: Rasouli
authors.affiliation: College of Health Sciences, University of Kentucky, Lexington, Kentucky;
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Peterson
authors.affiliation: Department of Medicine, Division of Endocrinology, and Barnstable Brown Diabetes and Obesity Center; University of Kentucky, Lexington, Kentucky; and philipkern@uky.edu.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kern
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D016000:Cluster Analysis; D049289:G(M2) Activator Protein / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D035683:MicroRNAs / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D024701:Myosin Type V / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000378:metabolism
chemical_list: D051722:ADAM Proteins; D049289:G(M2) Activator Protein; D007328:Insulin; D035683:MicroRNAs; D018995:Myosin Heavy Chains; D024701:Myosin Type V; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; C541010:MIRN145 microRNA, human; C528163:MIRN26 microRNA, human; C546086:MIRN30b microRNA, human; C495137:OLR1 protein, human; C077511:MYO5A protein, human; C498474:ADAM22 protein, human
keywords: adipose; insulin sensitivity; microRNA; microarray