title: Obesity Associated Modulation of miRNA and Co-Regulated Target Transcripts in Human Adipose Tissue of Non-Diabetic Subjects.
abstract: Micro RNAs (miRNAs) are a class of non-coding regulatory RNAs. We performed a transcriptome-wide analysis of subcutaneous adipose tissue and in vitro studies to identify miRNAs and co-regulated target transcripts associated with insulin sensitivity (SI) and obesity in human.
  
  
  
  We selected 20 insulin-resistant (IR, SI=2.0±0.7) and 20 insulin-sensitive (IS, SI=7.2±2.3) subjects from a cohort of 117 metabolically characterized non-diabetic Caucasians for comparison.
  
  
  
  After global profiling, 3 miRNAs had marginally different expressions between IR and IS subjects. A total of 14 miRNAs were significantly correlated with %fat mass, body mass index (BMI), or SI. The qRT-PCR validated the correlation of miR-148a-3p with BMI (r=-0.70, P=2.73X10(-6)). MiRNA target filtering analysis identified DNA methyltransferase 1 (DNMT1) as one of the target genes of miR-148a-3p. DNMT1 expression in adipose tissue was positively correlated with BMI (r=0.47, p=8.42X10(-7)) and was inversely correlated with miR-148a-3p (r=-0.34). Differentiation of SGBS preadipocytes showed up-regulation of miR-148a-3p and down-regulation of DNMT1 in differentiated adipocytes. After transfecting miR-148a-3p mimics into HeLa-S3 cells, DNMT1 was down-regulated, while transfection of adipose stem cells with miR-148a-3p inhibitor up-regulated DNMT1.
  
  
  
  Our results indicate that miR-148a-3pmediated regulation of DNMT1 expression may play a mechanistic role in obesity.
authors.forename: Neeraj K
authors.initials: NK
authors.lastname: Sharma
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Varma
authors.forename: Lijun
authors.initials: L
authors.lastname: Ma
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Hasstedt
authors.affiliation: Section on Endocrinology and Metabolism, Department of Internal Medicine Wake Forest School of Medicine, Medical Center Boulevard, NRC Building#E159 Winston-Salem, North Carolina 27157, USA. sdas@wakehealth.edu.
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Das
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000076123:DNA (Cytosine-5-)-Methyltransferase 1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; C000619380:DNMT1 protein, human