Adipogenic Human Adenovirus Ad-36 Induces Commitment, Differentiation and Lipid Accumulation in Human Adipose-derived Stem Cells

¹ Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808
² Obesity and Diabetes Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona
³ Obesity and Diabetes Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona; Baker Heart Research Institute, Melbourne, Australia
⁴ Wayne State University, Detroit, Michigan

^* To whom correspondence should be addressed. E-mail: nikhil.dhurandhar{at}pbrc.edu.

	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 - CEBP/, PPAR, aP2, 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 to 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.

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