Lack of Evidence for the Role of Human Adenovirus‐36 in Obesity in a European Cohort

Abstract

EpidEmiologyIn 2001, the possibility of an infectious component in the etiology of obesity was raised by Dhurandhar introducing the term "infectobesity" (1). In particular, support for Adenovirus type 36 (Ad-36) as a contributor to the obesity epidemic was found in chickens, mice and nonhuman primates (1-6). In 2005, a significant (relative risk = 2.7, P < 0.001) association between obesity and the presence of Ad-36 neutralizing antibodies in human serum was described in the United States by Atkinson et al. (7). Recently, subjects harboring Ad-36 DNA in their adipose tissue due to natural infection were described (8). To the best of our knowledge, very limited Ad-36 data in humans outside the United States are available, e.g., in Korean children as described by Atkinson et al. (9). Therefore our study explored this possible association in the Dutch and Belgian population data. Methods and ProceduresIn total, 509 serum samples of four groups of patients were analyzed for Ad-36 antibodies, including 128 Dutch health-care students, 131 Dutch obese patients (BMI range 27-40 kg/m 2 ), 127 Belgian twinmembers and 123 Belgian blood donors. The selected twin-members included 62 subjects with overweight (BMI >25 kg/m 2 ) and 65 lean subjects (BMI <21.5 kg/m 2 ). The presence of antibodies to Ad-36 in serum was determined using the "constant virus-decreasing serum" method and, according to Atkinson, the cutoff titer used to determine positivity was 1:8 (7).PCR was used to determine whether adenoviral DNA was present in visceral adipose tissue of 31 severely obese surgical patients of the Netherlands. After an in-house preliminary comparison of three different ways to extract a highest yield of total DNA from human visceral adipose tissue (data not shown), DNA was extracted from 10 mg adipose tissue using the MagnaLyser, Proteinase K, MagnaPure LC instrument and the total DNA extraction kit (Roche Diagnostics, Almere, the Netherlands). Prior to isolation, the adipose tissue was spiked with known concentrations of an extraction and amplification control. The real-time PCR used for quantification of Adenoviral DNA was based on primers described by Echavarria et al. (10), and detection of Ad-36 DNA was confirmed by testing reference Ad-36 ATCC strain VR-913 (data not shown). The quality of the assay was assured by positive and negative controls as well as a test on amplification inhibition in each sample by an external amplification control. The analytical sensitivity of the entire assay was determined as <5.0 adenoviral DNA copies per PCR.Statistical analysis including logistic regression analysis was performed using SPSS, version 15 (SPSS, Chicago, IL).The study was approved by the local ethics committee. resultsAn overall Ad-36 seroprevalence of 5.5% was found in 509 persons. In different patient subgroups, seroprevalence ranged Adenovirus infection has been shown to increase adiposity in chickens, mice, and nonhuman primates. Adenovirus type 36 (Ad-36) DNA was detected in adipose tissues in these animal trials. In the Uni...

Association of human adenovirus-36 in overweight Korean adults

“…In this regard, Ad-36 seropositivity increases from o5% in subjects up to 30 years of age to 410% in those over 50 years in the Netherlands and Belgium. 10 Nonetheless, we failed to find any increase in Ad-36 seropositivity in obese subjects with age (28.6% in schoolchildren and 30% in adults). At present, it is not known if an age-specific increase in Ad-36 seropositivity occurs only in normal Korean individuals.…”

“…A study of Dutch and Belgian people found that Ad-36 infection was unlikely to be associated with obesity. 10 Another recent study showed no association between Ad-36 seropositivity and US military personnel. 11 The reasons for these inconsistent results are not known.…”

Infectobesity: a New Area for Microbiological and Virological Research

“…These research studies provide considerable data to support infectobesity, but some studies do not agree with the concept, such as the Dutch and Belgian epidemiological studies (50).…”

“…Ad36 infection increases body weight, fat deposition, and insulin sensitivity, but decreases cholesterol and triglyceride levels (40,42,43). In contrast, several studies found no relationship between Ad36 seropositivity and human obesity, including, Dutch, Belgian (50), and USA military studies (51). All epidemiological studies of Ad36 are cross-sectional studies.…”

Possible Association of Altered Serum Lipids in Obese Adult Females with Adenoviral Infection

“…Obesity is a chronic disease with multiple etiology including also such non-dietary factors as a viral and bacterial infection [17,18,20,[23][24][25]. Recently, the evidences on the adenovirus infection related obesity where confirmed in adult patients from USA [26][27][28], Italy [28], Korea [29] and in pediatric subjects from Korea [30,31], but not fully validated association was observed in studies on Belgium and Dutch obese persons [32,33]. Thus, the aim of our pilot study was to investigate the possible role of human adenovirus infection in etiology of obesity in the sample cohort of adult female subjects recruited from typical middle-sized urban area in Poland.…”