Infectobesity: The role of adenoviruses in children obesity

Aim: Over the last 20 years, obesity was observed to increase 2-fold in adults and 3-fold in children, and spread all over the world like an epidemic. Diet and lifestyle-related behaviour changes are not sufficient to explain obesity epidemic, while infectious factors, particularly viruses should be considered, as well. It was reported that, some adenovirus serotypes [Adenovirus serotype 36 (Ad-36)] have been correlated with human obesity, while others (Ad-5 and Ad-37) with animal obesity, but other adenovirus serotypes displayed no correlation with obesity at all. In this present study, it was aimed to identify different adenovirus serotypes from clinical specimens collected from various centers, and by using these isolates, to demonstrate the role of adenoviruses in child obesity, also to investigate their correlation with serum lipid and leptin levels.Materials and Methods: The study was designed in two-steps. In the first stage of the trial, to determine adenovirus serotypes circulating in the community, also to identify adenoviruses to be further used in the micro-neutralization tests in the second stage of the study, adenovirus positive clinical specimens collected from Celal Bayar University (respiratory-blood, n=88), Kocaeli University (ophthalmic-environmental, n=94), and Ege University (ophthalmic-respiratory, n=18) were investigated by PCR method, and subsequently serotyping was performed by sequence analysis. Following DNA extraction from clinical specimens, amplification was carried out using the Adhex F1 and Adhex R1 primers described by Lu and Erdman. Clinical samples found positive by agarose gel electrophoresis were purified. Negative samples were tested by nested PCR. Sequences were determined using an ABI 310 sequence analyser and typed by BLAST analysis. Ad-5 and Ad-8 serotypes isolated from respiratory and eye swab samples, respectively, and Ad-36 (ATCC VR-1610) serotype obtained from LGC Standards were produced in cell cultures and stored at -80 ° C to be further used in the micro-neutralization tests. In the second stage of the trial, 10 ml blood samples were collected from totally 120 children, obese (n = 60) and nonobese (n = 60), who have admitted to Outpatient Clinic of Department of Pediatric Endocrine of Celal Bayar University. In these blood specimens, Adenovirus-specific IgG, IgA, IgM antibodies (Radim, Italy), and leptin levels (Invitrogen, USA) were tested by microEIA; HDL, LDL, triglyceride and cholesterol levels (Beckman Coulter, Ireland) by chemiluminescence; Ad-5, Ad-8, Ad-36 serotype-specific antibodies by micro-neutralization methods. T test and chi-square test were used in data analysis p?0.05 level was recognised as the level of significance.Results: Of the 200 clinical specimens obtained from three different centers, 84 were determined as adenovirus-positive, while 116 specimens were adenovirus-negative. 11 of the positive samples could not be typed by no means, while 60 samples (56 ophthalmic, 2 environmental, 2 respiratory) were identified as serotype 8, 7 samples (respiratory) as serotype 3, 4 samples (3 ophthalmic, 1 respiratory) as serotype 4 , and 2 samples (1 ophthalmic, 1 respiratory) as serotype 5.In obese group, rates of adenovirus IgM, IgG and IgA positive samples were respectively, 3.3%, 100% and 3.3%; however, in non-obese group, 8.3%, 93.3% and 5.0%, respectively. The rate of IgG positivity was found higher in obese group compared to non-obese group (p?0.05). HDL, LDL, cholesterol, triglyceride and leptin levels and mean ± SD values of obese subjects were found respectively as 44.6±10.2, 93.2±28.6, 159.5±34.7, 107.1±58.8, 373.5±262.3, while as 52.3±12.9, 84.8±23.9, 155.7±25.3, 96.8±42.0, 206.1±176.1 for non-obese subjects. In comparison to non-obese group, HDL values of the obese group were noted lower and leptin levels were found higer (p?0.05). In the obese group, the rates of Ad-36 and Ad-5 neutralizing antibody-positive subjects were found statistically significant compared to non-obese group (p?0.05); regarding the rate of Ad-8 neutralizing antibody-positivity, no significant correlation was observed between the two groups(p? 0.05).Conclusion: In our country, Adenovirus-related research studies are very limited, and furthermore, any study evaluating the relationship between Adenoviruses and obesity has not been conducted yet. According to our study data, Ad-5 and Ad-36 serotypes of Adenoviruses were determined to be associated with obesity in children. Our research is the first national study demonstrating the correlation between Ad-36 serotype and human obesity while the first international study pointing out the correlation between Ad-5 serotype and human obesity. Based on these reasons, we believe the data we achieved in this present study may have important contribution to both national and international literature.Keywords: Children, obesity, infection, adenoviruses.