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

Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA.
Stem Cells (Impact Factor: 6.52). 05/2008; 26(4):969-78. DOI: 10.1634/stemcells.2007-0868
Source: PubMed


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-CCAAT/Enhancer binding protein-beta, peroxisome proliferator-activated receptor-gamma, and fatty acid-binding protein-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 with 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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    • "In elucidating the similarity between our data and the aforementioned studies, as well as the pathophysiological processes at work, it has been suggested that a decrease in peripheral serum cholesterol and triglyceride levels is observed due to an increase in lipid storage, with the activation of inflammatory processes coupled with alterations in lipid metabolism (e.g., hyperplasia and hypertrophy of adipose tissues) seen in obese individuals infected with Ad-36 [16] [20] [36] [39] [40]. In this first reported clinical study from Turkey focusing on the Ad-36-obesity relationship in obese adults, however, we could not detect Ad-36 DNA in adipose tissue cells. "
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    ABSTRACT: Obesity which developes due to multifactorial reasons, was associated recently with human Adenovirus-36 (Ad-36). The aim of this study was to investigate the prevalence of Ad-36 antibodies in obese adults and also to investigate the DNA of Ad-36 in their adipose tissue. In this cross-sectional and case-control based study, 49 obese adults, with BMI ≥30 kg/m(2), and 49 non-obese adults, with BMI ≤25 kg/m(2), applied for esthetic purposes and were included in this study as patient and control groups, respectively. Adipose tissue samples, obtained by the lipoaspiration method, were studied by single-step PCR and nested-PCR methods. Simultaneously, the presence of Ad-36 antibodies and serum leptin and adiponectin levels were assessed by serum neutralization assay (SNA) and ELISA, respectively. Serum samples which didn't cause a cytopathic effect at ≥1:8 were accepted as positive. Ad-36 antibody was detected in 6 (12.2%) of 49 patients by SNA and was statistically significant (p < 0.05). Ad-36 DNA was not detected in any of the adipose tissue samples of the patient or control groups. Mean BMI and leptin levels were higher in the Ad-36-positive group, while adiponectin levels were found to be lower in the Ad-36-positive group. Although no statistically significant difference was found in cholesterol and triglyceride levels between the two groups (p > 0.05), lower mean serum cholesterol and triglyceride levels were found in the Ad-36-positive patients. In conclusion, we couldn't detect Ad-36 DNA in adipose tissue; however, we detected significantly higher Ad-36 antibody levels in the obese group compared to the non-obese group, according to the both univariant and multivariant analyses, suggesting that Ad-36 may play a role in obesity. There is a need for new and extended serial, particularly cohort and human-based, studies in order to have a clear understanding of the Ad-36-obesity relationship. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Feb 2015 · Microbial Pathogenesis
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    • "Among the leading contributing factors, such as genetic inheritance, behavior and environmental causes, in recent years viral infections have been considered as a possible cause of obesity. There are some reports suggesting a significant role of adenoviruses in the development of obesity [2] [3] [4] [5] [6] [7] [8] [9]. Adenoviruses are a large family of DNA viruses including at least 54 antigenic types of human adenoviruses. "
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    ABSTRACT: Background: Obesity is a chronic disease of multiple etiologies. Alongside the traditionally recognized causes of obesity, such as genetic inheritance and behaviour/environmental factors, in recent years adenoviral infections have been considered as a possible cause of obesity. Although numerous studies involving animals confirmed a strong relation between adenoviral infection and increased predisposition to obesity, an association of AdVs with human obesity has not been established conclusively. Objectives: The main aim of this study was to establish an association between seroprevalence of adenoviruses and obesity in the Polish population. Material and methods: Eighty-six subjects (both obese and non-obese) participated in this study. The presence and the concentration of typically non-specific antibodies to human adenoviruses in serum were determined using ELISA immunoassay. A serum lipid-profile was evaluated using commercial tests. Results: A total of 89.5% of subjects were positive for AdV-IgG (n = 77); 10.5% (n = 9) were negative. In non-obese or lean AdV-IgG positive subjects, the parameters as: body weight (63.5 vs. 57.0, p = 0.02), WHR (0.77 vs. 0.73, p = 0.02) and waist circumference (74.5 vs. 69.0, p = 0.01) were significantly higher as AdV-IgG negative individuals. Conclusions: We showed that there is an association between the presence of type unspecific anti-AdV antibodies in the serum and elevated body weight, BMI, WHR and waist circumference in lean and non-obese subjects from the Polish population.
    Full-text · Article · May 2014 · Advances in Clinical and Experimental Medicine
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    • "Ad36 infection accelerates the differentiation of preadipocytes to adipocytes in 3T3-L1 cells and human preadipocytes [13,27]. Although Ad36 E4orf1 gene is thought to be involved in the mechanism underlying virus-induced obesity, other related molecular factors are undetermined. "
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