title: Long-term inhibition of miR-21 leads to reduction of obesity in db/db mice.
abstract: OBJECTIVE
  To assess the effect of long-term pharmacological inhibition of miR-21 in a model of metabolic syndrome and obesity.
  
  
  METHODS
  Aged db/db mice were treated with locked nucleic acid-modified anti-miRs directed against miR-21 (LNA-21), control LNAs or PBS for 18 weeks. Cardiac function was assessed by echocardiography and the effect on body weight and white adipose tissue (WAT) was evaluated.
  
  
  RESULTS
  MiR-21 expression was efficiently inhibited in the heart and WAT with no apparent liver toxicity or deterioration of kidney function. MiR-21 inhibition had no effect on cardiac hypertrophy as well as systolic and diastolic cardiac functions. However, levels of cardiac collagen 1 were modestly reduced in LNA-21 treated mice. MiR-21 inhibition reduced body weight, as well as adipocyte size and serum triglycerides were significantly decreased. The miR-21 targets TGFβ-receptor 2 (TGFBR2) and phosphatase and tensin homolog (PTEN) were derepressed in WAT of LNA-21 treated mice and Sprouty1 and 2 were increased after miR-21 inhibition.
  
  
  CONCLUSIONS
  Long-term treatment with LNA-21 is safe and efficiently suppresses miR-21 expression. Cardiac function was not affected. LNA-21 treatment led to a significant weight loss and reduces adipocyte size as well as derepression of the targets TGFRB2, PTEN, and Sprouty1 and 2.
authors.affiliation: Institute for Cardiovascular Regeneration, Center of Molecular Medicine, University of Frankfurt, Frankfurt, Germany; Department of Cardiology, Internal Medicine III, University of Frankfurt, Frankfurt, Germany.
authors.forename: Timon
authors.initials: T
authors.lastname: Seeger
authors.forename: Ariane
authors.initials: A
authors.lastname: Fischer
authors.forename: Marion
authors.initials: M
authors.lastname: Muhly-Reinholz
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D024821:Metabolic Syndrome / Q000150:complications / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D009841:Oligonucleotides / Q000494:pharmacology
chemical_list: D035683:MicroRNAs; D009841:Oligonucleotides; C477371:locked nucleic acid; C531950:MIRN21 microRNA, mouse