Adipogenic human adenovirus ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells

Magdalena Pasarica, Nazar Mashtalir, Emily J. McAllister, Gail E. Kilroy, Juraj Koska, Paska Permana, Barbora De Courten, Minghuan Yu, Eric Ravussin, Jeffery M. Gimble, Nikhil V. Dhurandhar

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80 Scopus citations

Abstract

Human adenovirus Ad-36 is causatively and correlatively linked with animal and human obesity, respectively. Ad-36 enhances differentiation of rodent preadipocytes, but its effect on adipogenesis in humans is unknown. To indirectly assess the role of Ad-36-induced adipogenesis in human obesity, the effect of the virus on commitment, differentiation, and lipid accumulation was investigated in vitro in primary human adipose-derived stem/stromal cells (hASC). Ad-36 infected hASC in a time- and dose-dependent manner. Even in the presence of osteogenic media, Ad-36-infected hASC showed significantly greater lipid accumulation, suggestive of their commitment to the adipocyte lineage. Even in the absence of adipogenic inducers, Ad-36 significantly increased hASC differentiation, as indicated by a time-dependent expression of genes within the adipogenic cascade - CCAAT/Enhancer binding protein-β, peroxisome proliferator-activated receptor-γ, and fatty acid-binding protein - and consequentially increased lipid accumulation in a time- and viral dose-dependent manner. Induction of hASC to the adipocyte state by Ad-36 was further supported by increased expression of lipoprotein lipase and the accumulation of its extracellular fraction. hASC from subjects harboring Ad-36 DNA in their adipose tissue due to natural infection had significantly greater ability to differentiate compared with Ad-36 DNA-negative counterparts, which offers a proof of concept. Thus, Ad-36 has the potential to induce adipogenesis in hASC, which may contribute to adiposity induced by the virus.

Original languageEnglish
Pages (from-to)969-978
Number of pages10
JournalStem Cells
Volume26
Issue number4
DOIs
StatePublished - Apr 2008

Keywords

  • Adipocyte progenitors
  • Adipogenesis
  • Adiposity
  • Infectobesity
  • Lipogenesis
  • Obesity

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    Pasarica, M., Mashtalir, N., McAllister, E. J., Kilroy, G. E., Koska, J., Permana, P., De Courten, B., Yu, M., Ravussin, E., Gimble, J. M., & Dhurandhar, N. V. (2008). Adipogenic human adenovirus ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells. Stem Cells, 26(4), 969-978. https://doi.org/10.1634/stemcells.2007-0868