Obesity is a chronic condition with multiple causes, which has reached epidemic proportions in the U.S. The problem is compounded by a relative lack of effective treatments. Identifying and understanding various etiological factors involved may help in designing better treatments directed at the appropriate causes. Five viruses are reported to cause obesity in animal models, and viral infection may play an etiological role in some forms of human obesity. We recently reported adenovirus type-36 (Ad-36), the first human virus that increases adiposity in experimental animals including non-human primates and is associated with human obesity. Our in-vitro experiments with 3T3-L1 cells (rodent preadipocytes cell line) and human preadipocytes show Ad-36-induces up-regulation of fat cell differentiation and modulates the expression of several genes in fat cell differentiation pathway. Our central hypothesis is that up-regulation of fat cell differentiation contributes significantly to the adipogenic effect of Ad-36. The objective of this proposal is to identify the molecular interactions between fat cells and Ad-36, which will provide the basis to elucidate the mechanism of promotion of adipogenesis. Preliminary data suggested that the only a subset of viral genes are expressed in Ad-36 infected preadipocytes.
In Specific Aim 1, we will begin by identifying the Ad-36 transcription units expressed during differentiation of infected preadipocytes. From these candidates, the Specific Aim 2 will identify the viral transcription unit(s) that enhance preadipocyte differentiation. Next, the Specific Aim 3 will determine the differentiation-associated changes in cellular gene expression prompted by the candidate transcription unit identified in Specific Aim 2 as well as Ad-36 virus. Ad-2, a non-adipogenic human adenovirus will be used as a negative control. Also, genes found to enhance the differentiation of 3T3-L1 cells will be tested for their effect on differentiation of human preadipocytes. Identifying the interacting viral and cellular genes will help in future for elucidating novel signaling controls of fat cell differentiation and molecular pathway(s) for Ad-36 induced adiposity. Such an understanding of the mechanism of Ad-36 induced adiposity will help in determining the contribution of Ad-36 infections in human obesity. We believe that determining the role of viral infections in human obesity may influence the treatment, management, and possible prevention of such type of obesity. ? ?
|Dhurandhar, Emily J; Dubuisson, Olga; Mashtalir, Nazar et al. (2011) E4orf1: a novel ligand that improves glucose disposal in cell culture. PLoS One 6:e23394|
|Dubuisson, Olga; Dhurandhar, Emily J; Krishnapuram, Rashmi et al. (2011) PPARgamma-independent increase in glucose uptake and adiponectin abundance in fat cells. Endocrinology 152:3648-60|
|Rathod, Miloni A; Rogers, Pamela M; Vangipuram, Sharada D et al. (2009) Adipogenic cascade can be induced without adipogenic media by a human adenovirus. Obesity (Silver Spring) 17:657-64|
|McAllister, Emily J; Dhurandhar, Nikhil V; Keith, Scott W et al. (2009) Ten putative contributors to the obesity epidemic. Crit Rev Food Sci Nutr 49:868-913|
|Pasarica, Magdalena; Mashtalir, Nazar; McAllister, Emily J et al. (2008) Adipogenic human adenovirus Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells. Stem Cells 26:969-78|
|Pasarica, Magdalena; Loiler, Scott; Dhurandhar, Nikhil V (2008) Acute effect of infection by adipogenic human adenovirus Ad36. Arch Virol 153:2097-102|
|Rogers, P M; Fusinski, K A; Rathod, M A et al. (2008) Human adenovirus Ad-36 induces adipogenesis via its E4 orf-1 gene. Int J Obes (Lond) 32:397-406|
|Wang, Zhong Q; Cefalu, William T; Zhang, Xian H et al. (2008) Human adenovirus type 36 enhances glucose uptake in diabetic and nondiabetic human skeletal muscle cells independent of insulin signaling. Diabetes 57:1805-13|
|Rogers, Pamela M; Mashtalir, Nazar; Rathod, Miloni A et al. (2008) Metabolically favorable remodeling of human adipose tissue by human adenovirus type 36. Diabetes 57:2321-31|
|Pasarica, Magdalena; Dhurandhar, Nikhil V (2007) Infectobesity: obesity of infectious origin. Adv Food Nutr Res 52:61-102|
Showing the most recent 10 out of 13 publications