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I-S Yoon, S Park, R-H Kim, H L Ko, J-H Nam
Obesity impairs glycemic control and causes insulin resistance and type 2 diabetes. Adenovirus 36 (Ad36) infection can increase the uptake of excess glucose from blood into adipocytes by increasing GLUT4 translocation through the Ras-Akt signaling pathway, which bypasses PI3K-Akt-mediated insulin receptor signaling. E4orf1, a viral gene expressed early during Ad36 infection, is responsible for this insulin-sparing effect and may be an alternative target for improving insulin resistance. To deliver the gene to adipocytes only, we connected the adipocyte-targeting sequence (ATS) to the 5' end of E4orf1 (ATS-E4orf1)...
October 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Sangeeta P Bhat, Arun Sharma
Obesity, an impending global pandemic, is not being effectively controlled by current measures such as lifestyle modifications, bariatric surgery or available medications. Its toll on health and economy compels us to look for more effective measures. Fortunately, the advances in biology and molecular technology have been in our favour for delineating new pathways in the pathophysiology of obesity and have led to subsequent development of new drug targets. Development of anti-obesity drugs has often been riddled with problems in the past...
February 27, 2017: Current Drug Targets
Sayed Sartaj Sohrab, Mohammad A Kamal, Richard L Atkinson, Maha M Alawi, Esam I Azhar
BACKGROUND: The association of pathogenic viruses with obesity has now been well-known in both human and animals. Globally, human obesity has become a serious problem leading to the emergence of multiple lifethreatening diseases. Adenoviruses contribute a significant role in the induction of obesity by affecting various pathways. Due to impaired immunity, obese individuals are more prone to nosocomial infections leading to complications of obesity. In contrast, several other important factors contributing to human obesity are known...
2017: Current Drug Metabolism
Yi Jiao, Yiliyasi Aisa, Xiaodi Liang, Nuerbiye Nuermaimaiti, Xian Gong, Zhaoxia Zhang, Yaqun Guan
This study is to investigate the role of adenovirus 36 (Ad36) in regulating expression of peroxisome proliferator-activated receptor γ (PPARγ) and cell death-inducing DFFA-like effector c (CIDEC) in Ad36-induced adipocyte differentiation. Human adipose-derived mesenchymal stem cells (hAMSCs) were isolated and cultured, and then infected with Ad36. Ad36-induced adipocytes were identified using quantitative real-time PCR and Oil red O staining. The expression levels of PPARγ and CIDEC in Ad36-induced adipocytes were determined by quantitative real-time PCR and Western blot analysis...
April 2017: Molecular and Cellular Biochemistry
Travis B McMurphy, Wei Huang, Run Xiao, Xianglan Liu, Nikhil V Dhurandhar, Lei Cao
Considering that impaired proximal insulin signaling is linked with diabetes, approaches that enhance glucose disposal independent of insulin signaling are attractive. In vitro data indicate that the E4ORF1 peptide derived from human adenovirus 36 (Ad36) interacts with cells from adipose tissue, skeletal muscle, and liver to enhance glucose disposal, independent of proximal insulin signaling. Adipocyte-specific expression of Ad36E4ORF1 improves hyperglycemia in mice. To determine the hepatic interaction of Ad36E4ORF1 in enhancing glycemic control, we expressed E4ORF1 of Ad36 or Ad5 or fluorescent tag alone by using recombinant adeno-associated viral vector in the liver of three mouse models...
February 2017: Diabetes
Lili Huo, Jasmine Lyons, Dianna J Magliano
Over the last two decades, the prevalence of obesity has increased rapidly. While it is intuitively appealing to believe that the causes of obesity are manifestly related to excess dietary intake, combined with a reduced expenditure of energy via a decrease in physical activity, it is also been noted that the evidence for these as the sole causes of the obesity epidemic is incomplete. This has led to the search for other causes of obesity, particularly those which stem from the environment we live in. This review will explore two putative causes of obesity: infections and environmental pollutants...
September 2016: Current Obesity Reports
Vijay Hegde, Ha-Na Na, Olga Dubuisson, Susan J Burke, J Jason Collier, David Burk, Tamra Mendoza, Nikhil V Dhurandhar
AIMS: Exposure to human adenovirus Ad36 is causatively and correlatively linked with better glycemic control in animals and humans, respectively. Although the anti-hyperglycemic property of Ad36 may offer some therapeutic potential, it is impractical to use an infectious agent for therapeutic benefit. Cell-based studies identified that Ad36 enhances cellular glucose disposal via its E4orf1 protein. Ability to improve glycemic control in vivo is a critical prerequisite for further investigating the therapeutic potential of E4orf1...
February 2016: Biochimie
Sooho Park, Jihye Kim, Hye-Jung Shin, Young Mi Hong, Youn Ho Sheen, Hye-Lim Park, Hyun-Jung Jeon, Sun-Young Ahn, Jae-Hwan Nam
This study investigated the cross-sectional and longitudinal association between adenovirus 36 (Ad36) and obesity in 79 Korean adolescent boys over 1 year. We analyzed the changes in body composition and metabolic risk factors according to the presence of Ad36 antibodies. Ad36 antibodies in serum were detected using the constant virus-decreasing serum method. We found that the fat percentage and fasting insulin in the Ad36-seropositive group were greater than the Ad36-seronegative group. These results suggest that Ad36 infection is associated with an increase of adiposity, and the experience of Ad36 infection may affect the future fat gain of adolescents...
December 28, 2015: Journal of Microbiology and Biotechnology
S Park, H-L Park, S-Y Lee, J-H Nam
BACKGROUND: Various pathogens are implicated in the induction of obesity. Previous studies have confirmed that human adenovirus 36 (Ad36) is associated with increased adiposity, improved glycemic control and induction of inflammation. The Ad36-induced inflammation is reflected in the infiltration of macrophages into adipose tissue. However, the characteristics and role of adipose tissue macrophages (ATMs) and macrophage-secreted factors in virus-induced obesity (VIO) are unclear. Although insulin-like growth factor-1 (IGF-1) is involved in obesity metabolism, the contribution of IGF secreted by macrophages in VIO has not been studied...
March 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
N V Dhurandhar, D Bailey, D Thomas
There is evidence that certain infections may induce obesity. Obese persons may also have more severe infections and have compromised response to therapies. The objective of this study is to review the available literature identifying infections that potentially contribute to greater body mass index (BMI) and differential responses of overweight and obese persons to infections. A systematic literature review of human studies examining associations between infections and weight gain, differential susceptibility, severity, and response to prevention and treatment of infection according to BMI status (January 1980-July 2014) was conducted...
December 2015: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Jameson D Voss, Richard L Atkinson, Nikhil V Dhurandhar
UNLABELLED: Five human adenovirus subtypes, Ad5, Ad9, Ad31, Ad36, and Ad37, and a non-human adenovirus, SMAM1, are linked to increased adiposity in vitro or in vivo. Experimental infection with Ad5, Ad36, and Ad37 produced excess adiposity or weight gain in animals. Ad9 and Ad31 increase fat storage in tissue culture but are not associated with animal or human obesity. Ad36 is the most extensively studied adipogenic adenovirus and is correlated with some measure of overweight/obesity in humans from multiple countries...
November 2015: Reviews in Medical Virology
Ha-Na Na, Young-Mi Hong, Michael B Ye, Sooho Park, In-Beom Kim, Jae-Hwan Nam
Human adenovirus type 36 (Ad36) as an obesity agent induces adiposity by increasing glucose uptake and promoting chronic inflammation in fat tissues; in contrast, exercise reduces total body fat and inflammation. Our objective was to determine the association between Ad36 and the effects of exercise on inflammation and glycemic control. In the human trials (n = 54), Korean children (aged 12-14 years) exercised for 60 min on three occasions each week for 2 months. We compared the body mass index (BMI) Z-scores before and after exercise...
2014: PloS One
Ha-Na Na, Olga Dubuisson, Vijay Hegde, Jae-Hwan Nam, Nikhil V Dhurandhar
BACKGROUND: Aging and obesity are associated with elevated pro-inflammatory cytokines such as monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)α, which are linked to insulin resistance. Anti-inflammatory agents have marginal effect in improving insulin resistance. Hence, agents are needed to improve glycemic control despite the inflammation. Ad36, a human adenovirus, increases TNFα and MCP1 mRNA in adipose tissue, yet improves glycemic control in mice. Ad36 via its E4orf1 gene, up-regulates AKT/glucose transporter (Glut)-4 signaling to enhance cellular glucose uptake...
May 2016: Biochimie
Olga Dubuisson, Rena Sue Day, Nikhil V Dhurandhar
BACKGROUND: In children and adults, human adenovirus serotype 36 (Ad36) is linked with increased adiposity, and important metabolic alterations. Since this property is not shared by many other human adenovirus serotypes, it is imperative to specifically identify exposure to Ad36. Although serum neutralization assay (SNA) is the gold standard to specifically detect neutralizing antibodies (NA) to Ad36, it requires 2-weeks to complete and considerable training to interpret the results. Whereas, an enzyme-immuno assay (EIA) may provide a quicker and objective determination...
January 2015: Journal of Diabetes and its Complications
P K Berger, N K Pollock, E M Laing, S J Warden, K M Hill Gallant, D B Hausman, R A Tripp, L D McCabe, G P McCabe, C M Weaver, M Peacock, R D Lewis
CONTEXT: Although animal studies suggest that adenovirus 36 (Ad36) infection is linked to obesity and systemic inflammation, human data are scant and equivocal. OBJECTIVE: Associations of Ad36 infection with total body adiposity and inflammatory-related markers were determined in 291 children aged 9-13 years (50% female, 49% black). DESIGN: Fasting blood samples were measured for presence of Ad36-specific antibodies and TNF-α, IL-6, vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1)...
September 2014: Journal of Clinical Endocrinology and Metabolism
Yi Jiao, Xinmin Mao, Xi Chang, Kelimu Abudureyimu, Cheng Zhang, Jianfei Lu, Yanjiao Wang, Nuerbiye Nuermaimaiti, Yiliyasi Aisa, Xian Gong, Yaqun Guan
OBJECTIVE: This study is to determine if Adenovirus type 36 (Ad36) infection is related to macrophage infiltration in the obese group and non-obese group and the related molecular mechanisms. METHODS: Ninety obesity patients and 95 non-obesity Uygur individuals were enrolled in this study. CD68 levels in abdominal subcutaneous and omental adipose tissues were detected by immunohistochemistry. The cytokine expression levels of adiponectin (APMI) and visfatin in serum were measured by enzyme-linked immunosorbent assay...
2014: Diagnostic Pathology
H-N Na, J-H Nam
Human adenovirus 36 (Ad36) is positively associated with obesity in humans and animals. Ad36 infection is characterized by increased adiposity and inflammation. To investigate the possibility that a prophylactic vaccine candidate might protect against Ad36-induced obesity and inflammation, we purified Ad36 and ultraviolet-irradiated virus to obtain a vaccine candidate. After immunizing the mice with the vaccine candidate (vaccinated group), live Ad36 was injected into mice as a challenge test. Unvaccinated mice (control group) were immunized with phosphate-buffered saline and then challenged with live Ad36...
November 2014: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Ha-Na Na, Sooho Park, Hyun-Jung Jeon, Hyun-Bok Kim, Jae-Hwan Nam
Adenovirus 36 (Ad36) is known to be associated with human obesity and to trigger inflammation in murine models. However, to date no clinical drugs for treating virus-induced obesity have been developed. Therefore, in this study, the anti-obesity and anti-inflammation effects of mulberry extract on Ad36 were evaluated in mice. The mulberry extract-fed group showed a reduction in total body weight and in epidermal fat pads. A combination of various mulberry components (1-deoxynojirimycin, kuromanin chloride and resveratrol) and a mulberry extract prevented viral replication by 50% and 70%, respectively, compared with an untreated Ad36-infected group...
May 2014: Microbiology and Immunology
Qinglong Shang, Haiping Wang, Yujia Song, Lanlan Wei, Catharina Lavebratt, Fengmin Zhang, Hongxi Gu
OBJECTIVE: Serological studies on the relationship between adenovirus 36 (Ad36) and an increased risk of obesity development have shown conflicting results. We reviewed the published studies and carried out a meta-analysis to explore this relationship. METHODS: PubMed was searched until December 2012 for the relative references with sufficient information to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A total of 11 case-control studies, including 2508 obese subjects and 3005 controls, were selected...
March 2014: Obesity
J-H Nam, H-N Na, R L Atkinson, N V Dhurandhar
Human adenovirus Ad36 increases adiposity in several animal models, including rodents and non-human primates. Importantly, Ad36 is associated with human obesity, which has prompted research to understand its epidemiology and to develop a vaccine to prevent a subgroup of obesity. For this purpose, understanding the genomic stability of Ad36 in vivo and in vitro infections is critical. Here, we examined whether in vitro cell passaging over a 14-year period introduced any genetic variation in Ad36. We sequenced the whole genome of Ad36-which was plaque purified in 1998 from the original strain obtained from American Type Culture Collection, and passaged approximately 12 times over the past 14 years (Ad36-2012)...
February 2014: International Journal of Obesity: Journal of the International Association for the Study of Obesity
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