Adipogenic human adenovirus Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells.
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-beta, peroxisome proliferator-activated receptor-gamma, 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.
Pasarica
Magdalena
M
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA.
Mashtalir
Nazar
N
McAllister
Emily J
EJ
Kilroy
Gail E
GE
Koska
Juraj
J
Permana
Paska
P
de Courten
Barbora
B
Yu
Minghuan
M
Ravussin
Eric
E
Gimble
Jeffery M
JM
Dhurandhar
Nikhil V
NV
D000260:Adenoviruses, Human / Q000502:physiology*; D017667:Adipocytes / Q000166:cytology / Q000502:physiology / Q000821:virology*; D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology / Q000821:virology*; D000328:Adult; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D008055:Lipids / Q000502:physiology; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000166:cytology / Q000502:physiology / Q000821:virology*
D008055:Lipids