title: Targeting the circulating microRNA signature of obesity.
abstract: BACKGROUND
  Genomic studies have yielded important insights into the pathogenesis of obesity. Circulating microRNAs (miRNAs) are valuable biomarkers of systemic diseases and potential therapeutic targets. We sought to define the circulating pattern of miRNAs in obesity and examine changes after weight loss.
  
  
  METHODS
  We assessed the genomewide circulating miRNA profile cross-sectionally in 32 men and after surgery-induced weight loss in 6 morbidly obese patients. The most relevant miRNAs were cross-sectionally validated in 80 men and longitudinally in 22 patients (after surgery-induced weight loss). We evaluated the effects of diet-induced weight loss in 9 obese patients. Thirty-six circulating miRNAs were associated with anthropometric variables in the initial sample.
  
  
  RESULTS
  In the validation study, morbidly obese patients showed a marked increase of miR-140-5p, miR-142-3p (both P < 0.0001), and miR-222 (P = 0.0002) and decreased levels of miR-532-5p, miR-125b, miR-130b, miR-221, miR-15a, miR-423-5p, and miR-520c-3p (P < 0.0001 for all). Interestingly, in silico targets leukemia inhibitory factor receptor (LIFR) and transforming growth factor receptor (TGFR) of miR-140-5p, miR-142-3p, miR-15a, and miR-520c-3p circulated in association with their corresponding miRNAs. Moreover, a discriminant function of 3 miRNAs (miR-15a, miR-520c-3p, and miR-423-5p) was specific for morbid obesity, with an accuracy of 93.5%. Surgery-induced (but not diet-induced) weight loss led to a marked decrease of miR-140-5p, miR-122, miR-193a-5p, and miR-16-1 and upregulation of miR-221 and miR-199a-3p (P < 0.0001 for all).
  
  
  CONCLUSIONS
  Circulating miRNAs are deregulated in severe obesity. Weight loss-induced changes in this profile and the study of in silico targets support this observation and suggest a potential mechanistic relevance.
authors: Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona, Girona, Spain.
authors: Francisco José
authors: FJ
authors: Ortega
authors: Josep María
authors: JM
authors: Mercader
authors: Victoria
authors: V
authors: Catalán
authors: José María
authors: JM
authors: Moreno-Navarrete
authors: Neus
authors: N
authors: Pueyo
authors: Mónica
authors: M
authors: Sabater
authors: Javier
authors: J
authors: Gómez-Ambrosi
authors: Roger
authors: R
authors: Anglada
authors: José Antonio
authors: JA
authors: Fernández-Formoso
authors: Wifredo
authors: W
authors: Ricart
authors: Gema
authors: G
authors: Frühbeck
authors: José Manuel
authors: JM
authors: Fernández-Real
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood* / Q000235:genetics* / Q000601:surgery; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D035683:MicroRNAs