Human Adenovirus Ad-36 Promotes Weight Gain in Male Rhesus and Marmoset Monkeys

Dhurandhar, Nikhil V.; Whigham, Leah D.; Abbott, David H.; Schultz-Darken, Nancy; Israel, Barbara A.; Bradley, Steven M; Kemnitz, Joseph W.; Allison, David B.; Atkinson, Richard L.

doi:10.1093/jn/131.10.3155

Cited by 172 publications

(224 citation statements)

References 16 publications

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“…Of these, SMAM-1, an avian adenovirus was the first to show an association with human obesity 14 and Ad-36, a human adenovirus was the first human virus reported to cause adiposity in animal models and show association with human obesity. [1][2][3][4] As these initial reports, adipogenic potentials of more human adenoviruses, Ad-37 and Ad-5, have been reported. 6,15 Potential of various human adenoviruses to increase preadipocyte differentiation and cause adiposity may vary.…”

Section: Discussionmentioning

confidence: 82%

“…[1][2][3][4] Inoculation of 3T3-L1 preadipocytes with Ad-36, but not Ad-2 (a nonadipogenic human adenovirus), resulted in increased adipocyte number, cellular lipid accumulation and glycerol 3-phosphate dehydrogenase levels (GPDH; an adipocyte differentiation specific enzyme marker) and modulation of several key cellular genes of differentiation. 5 The absence of adipogenic effect of Ad-2 in animals and cells 5,6 and a lack of association with human obesity 1 suggested that the lipogenic potential is not a common characteristic of all adenoviruses.…”

Section: Introductionmentioning

confidence: 99%

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Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

Rathod

Vangipuram²,

Krishnan

et al. 2006

Int J Obes

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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.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

Rathod

Vangipuram²,

Krishnan

et al. 2006

Int J Obes

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“…This initial finding has now been extended to other species, including mice, primates, canine and possibly humans, with a range on animal and human viruses, including canine distemper virus, Rous-associated virus 7, Borna disease virus, SMAM-1 and Ad36. [5][6][7][8][9][10][11][12][13] In the present study, we have shown that the potential gene therapy viral vector Ad5 also leads to increase body adiposity in mice. Ad5-treated animals were shown to gain more weight over the 21 weeks following inoculation than saline-treated animals.…”

Section: Discussionmentioning

confidence: 95%

“…Increased adiposity has been observed in animal models following infection with animal viruses, canine distemper virus, [2][3][4][5] Rous-associated virus, 6,7 Borna virus, 8 an avian adenovirus, SMAM-1 9,10 and, also, with the human virus adenovirus 36 (Ad36). [11][12][13] Of these, SMAM-1 and Ad36 have been associated with human obesity: increased level of antibodies for these viruses has been found in human subjects who were obese. 14,15 Ad36 produces a syndrome of visceral obesity in chickens and mice, both hyperplastic and hypertrophic in nature.…”

Section: Introductionmentioning

confidence: 99%

Adiposity induced by adenovirus 5 inoculation

Herlihy

Bell

2005

Int J Obes

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OBJECTIVE:To investigate the effect of viral inoculation by adenovirus 5 (Ad5) on body composition in a mouse model. DESIGN: Longitudinal monitoring before and after a single injection of virus or saline. SUBJECTS: Two groups of CD1 mice, one group given a single intraperitoneal dose of Ad5 and the control group, saline. MEASUREMENTS: Bodyweights and food intake were recorded before and up to 21 weeks after inoculation. At the end of the study, whole-body 1 H magnetic resonance spectroscopy (MRS) and localised in vivo 1 H MRS spectroscopy of the liver was performed to assess whole-body adiposity and intrahepatic lipid content, respectively. RESULTS: Ad5-treated animals gained significantly more weight over a period of 21 weeks after inoculation than the controls, 21.8 g (18.8-25.0) and 18.8 g (17.3-19.8) respectively, (Po0.05). The gain in bodyweight in the former animals arises from increased deposition of adipose tissue as measured by whole-body 1 H MRS. Adiposity was 6.7% (3.10-11.20%), and 2.40% (0.85-5.65%) for the Ad5-treated and control animals, respectively (Po0.05). No significant difference in intrahepatic lipid content or food intake was observed between the two groups. CONCLUSION: The significantly higher percentage of adipose tissue in the Ad5-treated mice suggest viral infection may play a contributory role to a predisposition to obesity, although its contribution relative to other factors remains to be determined.

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“…17,18 Data from studies in animals indicate a possible role for virus infections in the etiology of human obesity. [19][20][21] Moreover, Ad-36 is associated with increased body weight and paradoxically lower cholesterol and triglyceride levels in Ad-36 antibody-positive vs -negative subjects. 22 Therefore it can be hypothesized that (chronic) virus infections induce adipocyte dysfunction thus leading to the development of diabetes mellitus and/or cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

Infection-induced inflammatory response of adipocytes in vitro

et al. 2008

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Background: Abdominal obesity plays an important role in the development of insulin resistance, diabetes mellitus and atherosclerosis. The exact pathophysiological mechanisms are unclear but adipocyte dysfunction is thought to be crucial. Infections are associated with the development of atherosclerosis as well as diabetes. In this study we investigated whether adipocytes can be infected and whether this results in production of inflammatory cytokines relevant for the development of atherosclerosis and diabetes. Methods: Pre-adipocytes were cultured and differentiated into mature adipocytes in vitro. Adipocytes and pre-adipocytes were incubated with infective and heat-inactivated Chlamydia pneumoniae, cytomegalovirus (CMV), adenovirus (Ad) subtypes 2 and 36, influenza A and respiratory syncitial virus (RSV). After 48 h, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a) and plasminogen activator inhibitor-1 (PAI-1) were measured in supernatants. Results: Infection of adipocytes with Ad-36, CMV and RSV resulted in increased IL-6 production from 192 ± 22 pg ml À1 (uninfected) to 1030 ± 86 pg ml À1 , 838 ± 59 pg ml À1 and 1241 ± 191 pg ml À1 , respectively (all Po0.01 vs control). In addition, Ad-36 infection slightly reduced PAI production in adipocytes (285 ± 26.8 ng ml À1 vs uninfected: 477 ± 71.2 ng ml À1 ; P ¼ 0.05) and pre-adipocytes (709±43.3 ng ml À1 vs uninfected: 1071±71.8 ng ml À1 ; Po0.01). In contrast, human Ad type 2 did not exert any effect on IL-6 or PAI production. None of the microorganisms induced significant changes in adiponectin and/or TNF-a production. Conclusions: Adipocytes can be infected with several microorganisms in vitro. Infection of adipocytes with Ad-36, but not Ad-2 leads to increased production of IL-6 which might contribute to chronic low-grade inflammation, a process known to be involved in the development of cardiovascular diseases and type 2 diabetes.

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Human Adenovirus Ad-36 Promotes Weight Gain in Male Rhesus and Marmoset Monkeys

Cited by 172 publications

References 16 publications

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

Adiposity induced by adenovirus 5 inoculation

Infection-induced inflammatory response of adipocytes in vitro

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