Identification of the adipogenic genes of Adenovirus 36

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DESCRIPTION (provided by applicant): Obesity has become a major health problem in the United States. Although many of the possible causes of obesity are under intensive investigation, the role of infectious agents has been not been well studied. Human adenovirus type 36 (Ad-36) has been shown to cause excessive weight gain and adiposity in several animal models (mice, marmosets, chickens) and is linked to obesity in seroepidemiological studies of humans. Ad-36 also accelerates the differentiation of 3T3-L1 preadipocytes to adipocytes in cell culture. The purpose of this study is to identify the Ad-36 gene (or genes) required for this effect. In Aim 1, retroviral vectors will be used to produce 3T3-L1 cell lines constitutively expressing various Ad-36 open reading frames. The effect of these Ad-36 genes on adipocytic differentiation will be determined. In Aim 2, the regulatory pathways affected by the adipogenic Ad-36 gene will be identified. Western blot analysis will be used to determine protein levels and phosphorylation state. Fluorescence microscopy will be used to determine protein localization. In Aim 3, human preadipocytes will be transduced with lentiviral vectors expressing the adipogenic Ad-36 gene to determine its effects on human preadipocyte differentiation.