Adaptive expression of microRNA-125a in adipose tissue in response to obesity in mice and men

• Published in: PloS one Vol. 9; no. 3; p. e91375
• Main Authors: Diawara, Malika R, Hue, Christophe, Wilder, Steven P, Venteclef, Nicolas, Aron-Wisnewsky, Judith, Scott, James, Clément, Karine, Gauguier, Dominique, Calderari, Sophie
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.03.2014; Public Library of Science (PLoS)
• Subjects: 3T3-L1 Cells; Adaptation, Biological - genetics; Adipocytes; Adipocytes - metabolism; Adipose tissue; Adipose Tissue - metabolism; Adult; Aged; Aged, 80 and over; Analysis; Animals; Bariatric Surgery; Biology and Life Sciences; Biomarkers; Biopsy; Body fat; Body mass index; Cell Differentiation; Cluster Analysis; Computer and Information Sciences; Diabetes; Diet, High-Fat; Down-Regulation; Embryos; Enrichment; Female; Gastric bypass; Gastrointestinal surgery; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene set enrichment analysis; Genes; Genome-Wide Association Study; Genomes; Genomics; Glucose; Glucose - metabolism; High fat diet; House mouse; Human health and pathology; Humans; Insulin; Insulin Resistance; Life Sciences; Male; Mannan; Mannose-binding lectin; Medicine and Health Sciences; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; Middle Aged; miRNA; Nutrition research; Obesity; Obesity - diagnosis; Obesity - genetics; Obesity - metabolism; Obesity - surgery; Pathogenesis; Patients; Phenotype; Physiology; Proteins; Research and Analysis Methods; Ribonucleic acid; RNA; RNA Interference; Serine; Serine peptidase; Sex Factors; Surgery; Thyrotroph embryonic factor; Transcriptome; Triglycerides; Type 2 diabetes; Ubiquitin; Ubiquitin-conjugating enzyme; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0091375

MicroRNAs are emerging as new mediators in the regulation of adipose tissue biology and the development of obesity. An important role of microRNA-125a has been suggested in the pathogenesis of insulin resistance (IR). Here, we characterized the function of microRNA-125a in adipose tissue in a context of experimentally-induced IR and obesity in mice and in obese patients. We showed time dependent overexpression of the microRNA in adipose tissue of BALB/c and C57BL/6J mice in response to high fat diet (HFD) feeding. MicroRNA-125a expression was downregulated in vitro in insulin resistant 3T3-L1 adipocytes and ex vivo in adipose tissue of obese patients. In vitro modulation of microRNA-125a expression in 3T3-L1 adipocytes did not affect glucose uptake. Gene set enrichment analysis (GSEA) identified significantly altered expression patterns of predicted microRNA-125a gene targets in transcriptomic datasets of adipose tissue from HFD-fed mice and obese patients. Among genes that contributed to global enrichment of altered expression of microRNA-125a targets, Thyrotroph embryonic factor (Tef), Mannan-binding lectin serine peptidase 1, Reticulon 2 and Ubiquitin-conjugating enzyme E2L3 were significantly differentially expressed in adipose tissue in these groups. We showed that Tef expression is reduced in adipose tissue of obese patients following gastric bypass surgery. Our findings indicate that microRNA-125a expression in adipose tissue adapts to IR and may play a role in the development of obesity in mice and obese subjects through uncoupled regulation of the expression of microRNA-125a and its targets.