title: Human adenovirus 36 decreases fatty acid oxidation and increases de novo lipogenesis in primary cultured human skeletal muscle cells by promoting Cidec/FSP27 expression.
abstract: BACKGROUND
  It has been well documented that human adenovirus type 36 (Ad-36) is associated with obesity. However, the underlying molecular mechanism of Ad-36 inducing obesity remains unknown. We sought to investigate the effect of Ad-36 infection on Cidec, AMPK pathway and lipid metabolism in primary cultured human skeletal muscle cells.
  
  
  METHODS
  Cidec/fat-specific protein 27 (FSP27), fatty acid oxidation, AMPK signaling and the abundance of proteins involved in lipid synthesis were determined in muscle cells infected with various doses (1.9-7.6 MOI) of Ad-36 and non-lipogenic adenovirus type 2 (Ad-2) as a negative control as well as an uninfected control. Cidec/FSP27 siRNA transfection was performed in Ad-36-infected muscle cells.
  
  
  RESULTS
  Our data show that Ad-36 significantly reduced fatty acid oxidation in a dose-dependent manner (all P values are <0.01), but Ad-2 did not affect fatty acid oxidation. Ad-36 substantially increased Cidec/FSP27, ACC, sterol regulatory element-binding protein 1c (SREBP-1c), SREBP-2 and 3-hydroxy-3-methylglutaryl-CoA reductase protein abundance, but significantly reduced AMPK activity, mitochondrial mass and uncoupling protein 3 (UCP3) abundance in comparison with control cells (all P values are <0.01). Oil Red O staining revealed that there was substantial fat accumulation in the Ad-36-infected muscle cells. Furthermore, Cidec/FSP27 siRNA transfection significantly reduced FSP27 expression and partially restored AMPK signaling, increased UCP3 and decreased SERBP 1c and perilipin proteins in Ad-36-infected muscle cells. Interestingly, neither Ad-36 nor Ad-2 affected peroxisome proliferator-activated receptor γ protein expression in muscle cells.
  
  
  CONCLUSIONS
  This study suggests that Ad-36 induced lipid droplets in the cultured skeletal muscle cells and this process may be mediated by promoting Cidec/FSP27 expression.
authors.affiliation: Diabetes and Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA. wangzq@PBRC.edu
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: X H
authors.initials: XH
authors.lastname: Zhang
authors.forename: E Z
authors.initials: EZ
authors.lastname: Floyd
authors.forename: W T
authors.initials: WT
authors.lastname: Cefalu
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins; D002478:Cells, Cultured; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D050155:Lipogenesis / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000821:virology; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D010084:Oxidation-Reduction; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; C472088:CIDEC protein, human; D005227:Fatty Acids; D011506:Proteins