Adenovirus-36 is associated with obesity in children and adults in Sweden as determined by rapid ELISA

Abstract

Background: Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/The Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals.

Principal findings: Using a novel ELISA, 1946 clinically well-characterized individuals including 424 children and 1522 non-diabetic adults, and 89 anonymous blood donors, residing in central Sweden representing the population in Stockholm area, were studied for the presence of antibodies against Adv36 in serum. The prevalence of Adv36 positivity in lean individuals increased from ∼7% in 1992-1998 to 15-20% in 2002-2009, which paralleled the increase in obesity prevalence. We found that Adv36-positive serology was associated with pediatric obesity and with severe obesity in females compared to lean and overweight/mildly obese individuals, with a 1.5 to 2-fold Adv36 positivity increase in cases. Moreover, Adv36 positivity was less common among females and males on antilipid pharmacological treatment or with high blood triglyceride level. Insulin sensitivity, measured as lower HOMA-IR, showed a higher point estimate in Adv36-positive obese females and males, although it was not statistically significant (p = 0.08).

Conclusion: Using a novel ELISA we show that Adv36 infection is associated with pediatric obesity, severe obesity in adult females and lower risk of high blood lipid levels in non-diabetic Swedish individuals.

Figure 1. Distribution of BMI in analyzed children and adults.

A) Distribution of BMI SDS (BMI Z-Score) adjusted for age and gender according to Rolland-Cachera et al, 1982 among lean (BMI SDS: −1.4−1.8) and overweight/obese (BMI SDS: 2.2–10.5) children; B) Distribution of BMI in the lean (BMI<25 kg/m²), overweight and mildly obese (28<BMI<35 kg/m²), and severely obese (BMI≥35 kg/m²) adults studied; C) BMI-SDS distribution of those children positive for Adv36 in ELISA; D) BMI-distribution of those adults positive for Adv36 in ELISA.

Figure 2. ELISA titration curve.

ELISA titration curve of serum from rabbit inoculated with Adv36. Cutoff for positivity in the ELISA is at rabbit serum dilution 1∶1280 (OD₄₅₀ = 0.12), that is in the low linear region. The average optical density at 450 nm of three experiments, each in duplicate, from one rabbit is shown. Error bars indicate SEM. Similar data were obtained from two additional rabbits.

Figure 3. Prevalence of Adv36 in lean Swedes.

Prevalence of positive Human adenovirus-36 serology in serum samples from adults and children living in Stockholm and Uppsala, Sweden, between 1992/1998 and 2009. The Adv36 serology was determined using the Adv36-ELISA. Error bars indicate standard error of proportion.

Figure 4. Association between Adv36 and obesity.

A) Higher proportion of children with positive Adv36 serology among pediatric obesity patients (BMI SDS: 2.2–10.5) than lean (BMI SDS: −1.4−1.8) children from high schools in Stockholm. B) Higher prevalence of positive Adv36 serology among severely obese (BMI≥35 kg/m²) females compared to lean (BMI<25 kg/m²) and overweight/mildly obese (O.w./mild obese) (28<BMI<35 kg/m²) females in Stockholm and Uppsala. Error bars indicate standard error of proportion. Due to a low number of severely obese males (n = 11), Adv36 association to severe obesity in males could not be analyzed. However, no difference in Adv36 positivity was found between females and males in lean and overweight/mildly obese groups, and no difference in prevalence of Adv36 positivity was detected among males between lean and overweight/mildly obese.