title: Human adenovirus Ad-36 induces adipogenesis via its E4 orf-1 gene.
abstract: OBJECTIVE
  Understanding the regulation of adipocyte differentiation by cellular and extracellular factors is crucial for better management of chronic conditions such as obesity, insulin resistance and lipodystrophy. Experimental infection of rats with a human adenovirus type 36 (Ad-36) improves insulin sensitivity and promotes adipogenesis, reminiscent of the effect of thiozolinediones. Therefore, we investigated the role of Ad-36 as a novel regulator of the adipogenic process.
  
  
  RESULTS
  Even in the absence of adipogenic inducers, infection of 3T3-L1 preadipocytes and human adipose-derived stem cells (hASC) by Ad-36, but not Ad-2 that is another human adenovirus, modulated regulatory points that spanned the entire adipogenic cascade ranging from the upregulation of cAMP, phosphatidylinositol 3-kinase and p38 signaling pathways, downregulation of Wnt10b expression, and increased expression of CCAAT/enhancer binding protein-beta and peroxisome proliferator-activated receptor gamma2 and consequential lipid accumulation. Next, we identified that E4 open reading frame (orf)-1 gene of the virus is necessary and sufficient for Ad-36-induced adipogenesis. Selective knockdown of E4 orf-1 by RNAi abrogated Ad-36-induced adipogenic signaling cascade in 3T3-L1 cells and hASC. Compared to the null vector, selective expression of Ad-36 E4 orf-1 in 3T3-L1 induced adipogenesis, which was abrogated when the PDZ-binding domain of the protein was deleted.
  
  
  CONCLUSIONS
  Thus, Ad-36 E4 orf-1 is a novel inducer of rodent and human adipocyte differentiation process.
authors.affiliation: Department of Infections and Obesity, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA. nikhil.dhurandhar@pbrc.edu
authors.forename: P M
authors.initials: PM
authors.lastname: Rogers
authors.forename: K A
authors.initials: KA
authors.lastname: Fusinski
authors.forename: M A
authors.initials: MA
authors.lastname: Rathod
authors.forename: S A
authors.initials: SA
authors.lastname: Loiler
authors.forename: M
authors.initials: M
authors.lastname: Pasarica
authors.forename: M K
authors.initials: MK
authors.lastname: Shaw
authors.forename: G
authors.initials: G
authors.lastname: Kilroy
authors.forename: G M
authors.initials: GM
authors.lastname: Sutton
authors.forename: E J
authors.initials: EJ
authors.lastname: McAllister
authors.forename: N
authors.initials: N
authors.lastname: Mashtalir
authors.forename: J M
authors.initials: JM
authors.lastname: Gimble
authors.forename: T C
authors.initials: TC
authors.lastname: Holland
authors.forename: N V
authors.initials: NV
authors.lastname: Dhurandhar
mesh_terms: D041721:3T3-L1 Cells; D000260:Adenoviruses, Human / Q000235:genetics*; D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation; D006801:Humans; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000502:physiology; D051381:Rats
chemical_list: D009856:Oncogene Proteins, Viral