Open AccessAdipogenic Human Adenovirus Ad‐36 Induces Commitment, Differentiation, and Lipid Accumulation in Human Adipose‐Derived Stem Cells
Author(s) -
Pasarica Magdalena,
Mashtalir Nazar,
McAllister Emily J.,
Kilroy Gail E.,
Koska Juraj,
Permana Paska,
de Courten Barbora,
Yu Minghuan,
Ravussin Eric,
Gimble Jeffery M.,
Dhurandhar Nikhil V.
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0868
Subject(s) - adipogenesis , biology , adipose tissue , adipocyte , stem cell , medicine , microbiology and biotechnology , endocrinology , cellular differentiation , multipotent stem cell , stromal vascular fraction , mesenchymal stem cell , progenitor cell , biochemistry , gene
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. Disclosure of potential conflicts of interest is found at the end of this article.