Original Article
International Journal of Obesity (2007) 31, 78–86. doi:10.1038/sj.ijo.0803358; published online 2 May 2006
Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes
M Rathod1,2,4, S D Vangipuram1,4, B Krishnan2, A R Heydari1, T C Holland3 and N V Dhurandhar2
- 1Department of Nutrition and Food Science, Detroit, Michigan, USA
- 2Department of Viruses and Obesity, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA
- 3Department of Immunology and Pathology, Wayne State University, Detroit, Michigan, USA
Correspondence: Dr NV Dhurandhar, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA. E-mail: Nikhil.dhurandhar@pbrc.edu
4These two authors contributed equally to this work.
Received 18 November 2005; Revised 18 February 2006; Accepted 27 February 2006; Published online 2 May 2006.
Abstract
Objective:
Human adenovirus Ad-36 causes adiposity in animal models and shows association with human obesity. Ad-36 enhances differentiation of 3T3-L1 and human preadipocytes, without cell lysis, a characteristic that may contribute to its adipogenic effect observed in vivo. Ad-2, another human adenovirus is nonadipogenic in animals and in 3T3-L1 cells and shows no correlation with human obesity. The objective of this study was to determine the adipogenic roles of viral mRNA and DNA, which may explain the differential effects of Ad-36 and Ad-2 on preadipocyte differentiation.
Methods:
This study determined the duration of selected Ad-36 gene expression in 3T3-L1 cells, and the effect on preadipocytes differentiation, when Ad-36 gene expression was attenuated by Cidofovir, an antiadenoviral agent.
Results:
The results showed that Ad-36, but not Ad-2, expresses viral mRNA. Ad-36 gene expression peaked at 2–4 days postinoculation and very low levels persisted after day 7. Despite the viral mRNA expression, Ad-36 infection of 3T3-L1 cells was abortive as indicated by a progressive decrease in viral DNA quantity. Attenuation of Ad-36 mRNA expression by Cidofovir reduced the adipogenic effect of the virus.
Conclusion:
In conclusion, viral mRNA expression, although transient, is a prerequisite for enhancing differentiation of preadipocytes by Ad-36. Viral DNA replication was not required for the effect. This is the first evidence for the role of gene expression of an adipogenic human virus in enhancing preadipocytes differentiation. This study provides the basis for further understanding novel regulatory modulators of preadipocytes differentiation.
Keywords:
obesity, adiposity, 3T3-L1, E1A, E4 orf1, Cidofovir, antiviral, C/EBP 
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