title: MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity.
abstract: OBJECTIVE
  We investigated the regulation and involvement of microRNAs (miRNAs) in fat cell development and obesity.
  
  
  METHODS
  Using miRNA microarrays, we profiled the expression of >370 miRNAs during adipogenesis of preadipocyte 3T3-L1 cells and adipocytes from leptin deficient ob/ob and diet-induced obese mice. Changes in key miRNAs were validated by RT-PCR. We further assessed the contribution of the chronic inflammatory environment in obese adipose tissue to the dysregulated miRNA expression by tumor necrosis factor (TNF)-alpha treatment of adipocytes. We functionally characterized two adipocyte-enriched miRNAs, miR-103 and miR-143, by a gain-of-function approach.
  
  
  RESULTS
  Similar miRNAs were differentially regulated during in vitro and in vivo adipogenesis. Importantly, miRNAs that were induced during adipogenesis were downregulated in adipocytes from both types of obese mice and vice versa. These changes are likely associated with the chronic inflammatory environment, since they were mimicked by TNF-alpha treatment of differentiated adipocytes. Ectopic expression of miR-103 or miR-143 in preadipocytes accelerated adipogenesis, as measured both by the upregulation of many adipogenesis markers and by an increase in triglyceride accumulation at an early stage of adipogenesis.
  
  
  CONCLUSIONS
  Our results provide the first experimental evidence for miR-103 function in adipose biology. The remarkable inverse regulatory pattern for many miRNAs during adipogenesis and obesity has important implications for understanding adipose tissue dysfunction in obese mice and humans and the link between chronic inflammation and obesity with insulin resistance.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
authors.forename: Huangming
authors.initials: H
authors.lastname: Xie
authors.forename: Bing
authors.initials: B
authors.lastname: Lim
authors.forename: Harvey F
authors.initials: HF
authors.lastname: Lodish
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D035683:MicroRNAs / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D035683:MicroRNAs; C455622:PPARGC1B protein, human; D016601:RNA-Binding Proteins; D014280:Triglycerides