title: Expression Pattern and Regulatory Role of microRNA-23a in Conjugated Linoleic Acids-Induced Apoptosis of Adipocytes.
abstract: OBJECTIVE
  Conjugated linoleic acids (CLAs) are known to induce apoptosis in adipocytes; however, the cellular mechanisms involved remained illdefined. We explored the different apoptotic induction effects of two CLA isomers on adipocytes and then investigated the expression and function of microRNAs (miRNAs) related to the apoptosis.
  
  
  METHODS
  TUNEL and FCM assays were used to detect CLAs-induced adipocyte apoptosis. Microarrays were used to compare the differential expression of miRNAs. MiR-23a, a miRNA that showed significant changes in expression in the CLA-treated cells, was selected for the subsequent functional studies via over-expression and knock down in in vivo and in vitro experiments.
  
  
  RESULTS
  C9, t11-CLA exhibited a stronger induction of apoptosis in the differentiated 3T3-L1 adipocytes than t10, c12-CLA. However, t10, c12-CLA could rapidly activate NF-κB, which may have caused their different apoptotic effects. MiR-23a was markedly down-regulated by the CLAs treatment and miR-23a over-expression attenuated CLA-induced apoptosis. Apoptosis protease-activating factor 1 (APAF1) was identified as a target gene of miR-23a. In an in vivo experiment endogenous miR-23a was down-regulated in mice fed with a mixture of both CLAs. The mice also exhibited less fat deposition and more apoptotic fat cells in adipose tissue. Moreover, endogenous miR-23a was suppressed in mice via intravenous injection with an antagomir which resulted in decreased body weight, increased number of apoptotic fat cells and increased APAF1 expression in adipose tissue.
  
  
  CONCLUSIONS
  Taken together, our results suggest that miR-23a plays a critical role in CLA-induced apoptosis in adipocytes via controlling APAF1 expression.
authors.affiliation: Chongqing Academy of Animal Science Rongchang, China.
authors.forename: Renli
authors.initials: R
authors.lastname: Qi
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Huang
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.forename: Zuohua
authors.initials: Z
authors.lastname: Liu
authors.forename: Feiyun
authors.initials: F
authors.lastname: Yang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D020869:Gene Expression Profiling; D020868:Gene Silencing / Q000187:drug effects; D007536:Isomerism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D044243:Linoleic Acids, Conjugated; D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D016328:NF-kappa B