A Human Adenovirus Enhances Preadipocyte Differentiation

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Abstract
Adenovirus 36 (Ad-36) has been shown to increase adiposity in experimentally infected chickens, mice, and marmosets (nonhuman primates). Neutralizing antibodies to Ad-36 are associated with obesity in humans. The metabolic and molecular mechanisms responsible for Ad-36-induced adipogenesis are unknown. As a potential adipogenic mechanism, this study examined if Ad-36 enhanced differentiation of preadipocytes. To determine the suitability of 3T3-L1 cells (murine preadipocyte cell line) as a model, the first experiment determined if Ad-36 attaches and initiates replication in the cells. Next, effects of Ad-36 on the number of differentiated adipocytes, glycerol 3-phosphate dehydrogenase (GPDH) levels, and cellular lipid accumulation were determined. The last experiment determined the effect of Ad-36 on human primary preadipocyte differentiation. Ad-2, a known nonadipogenic human adenovirus, was used as a negative control in these experiments. Immunofluorescence studies showed adenoviral attachment to 3T3-L1 cells, and reverse transcriptase-polymerase chain reaction showed expression of the Ad-36 E1A gene in the infected cells. Ad-36, but not Ad-2, increased the number of differentiated adipocytes, GPDH enzyme levels, and the total cellular lipid content. Also, Ad-36, but not Ad-2, increased GPDH levels in human preadipocytes. Taken together, these experiments showed that Ad-36 enhanced differentiation of preadipocytes, which may be a contributory mechanism to its adipogenic effect in vivo. The lack of effect of Ad-2 on differentiation demonstrated that the observed findings were not a common characteristic of all adenoviruses. Future understanding of the molecular interactions of cellular and viral genes responsible for enhanced differentiation may reveal novel signaling pathways and controls of preadipocyte differentiation.