title: Adaptive expression of microRNA-125a in adipose tissue in response to obesity in mice and men.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS 872, Cordeliers Research Center, University Pierre & Marie Curie, Paris, France; Institute of Cardiometabolism & Nutrition, ICAN, Pitié-Salpêtrière Hospital, University Pierre & Marie-Curie, Paris, France.
authors.forename: Malika R
authors.initials: MR
authors.lastname: Diawara
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS 872, Cordeliers Research Center, University Pierre & Marie Curie, Paris, France; Institute of Cardiometabolism & Nutrition, ICAN, Pitié-Salpêtrière Hospital, University Pierre & Marie-Curie, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hue
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Wilder
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS 872, Cordeliers Research Center, University Pierre & Marie Curie, Paris, France; Institute of Cardiometabolism & Nutrition, ICAN, Pitié-Salpêtrière Hospital, University Pierre & Marie-Curie, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Venteclef
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS 872, Cordeliers Research Center, University Pierre & Marie Curie, Paris, France; Institute of Cardiometabolism & Nutrition, ICAN, Pitié-Salpêtrière Hospital, University Pierre & Marie-Curie, Paris, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Aron-Wisnewsky
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Scott
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS 872, Cordeliers Research Center, University Pierre & Marie Curie, Paris, France; Institute of Cardiometabolism & Nutrition, ICAN, Pitié-Salpêtrière Hospital, University Pierre & Marie-Curie, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS 872, Cordeliers Research Center, University Pierre & Marie Curie, Paris, France; Institute of Cardiometabolism & Nutrition, ICAN, Pitié-Salpêtrière Hospital, University Pierre & Marie-Curie, Paris, France; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauguier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS 872, Cordeliers Research Center, University Pierre & Marie Curie, Paris, France; Institute of Cardiometabolism & Nutrition, ICAN, Pitié-Salpêtrière Hospital, University Pierre & Marie-Curie, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Calderari
mesh_terms: D041721:3T3-L1 Cells; D000220:Adaptation, Biological / Q000235:genetics*; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D050110:Bariatric Surgery; D015415:Biomarkers; D002454:Cell Differentiation; D016000:Cluster Analysis; D059305:Diet, High-Fat; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D010641:Phenotype; D034622:RNA Interference; D012737:Sex Factors; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; D005947:Glucose