TY - JOUR
T1 - Adipogenic human adenovirus Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells
AU - Pasarica, Magdalena
AU - Mashtalir, Nazar
AU - McAllister, Emily J
AU - Kilroy, Gail E
AU - Koska, Juraj
AU - Permana, Paska A
AU - de Courten, Barbora
AU - Yu, Minghuan
AU - Ravussin, Eric
AU - Gimble, Jeffery
AU - Dhurandhar, Nikhil
PY - 2008
Y1 - 2008
N2 - 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- , peroxisome
proliferator-activated receptor- , 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.
AB - 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- , peroxisome
proliferator-activated receptor- , 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.
UR - http://onlinelibrary.wiley.com/doi/10.1634/stemcells.2007-0868/pdf
U2 - 10.1634/stemcells.2007-0868
DO - 10.1634/stemcells.2007-0868
M3 - Article
SN - 1066-5099
VL - 26
SP - 969
EP - 978
JO - Stem Cells
JF - Stem Cells
IS - 4
ER -
