Associations of adenovirus 36 infection with inflammation, adiposity, and bone strength

Abstract

Though animal and cell culture studies suggest that adenovirus 36 is linked to inflammation, obesity, and osteoporosis, human data are scant. The purpose of this research was to determine associations of Ad36 seropositivity [Ad36(+)], inflammatory-related markers, adiposity, and bone strength in children. The first study (Chapter 3) addressed relationships of Ad36(+), serum inflammatory-related markers, and fat mass, assessed by dual-energy X-ray absorptiometry, in 291 children ages 9-13 years. There was a higher prevalence of Ad36(+) in the highest tertiles of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) compared to their respective middle and lowest tertiles (both P<0.03). There was also a trend toward a higher prevalence of Ad36(+) in the highest tertile of vascular endothelial growth factor (VEGF) compared to tertiles 1 and 2 (P=0.05). Multinomial logistic regression, adjusting for age, race, sex, and fat-free soft tissue (FFST) mass, revealed that compared to participants with the lowest concentrations of TNF-α, IL-6, and VEGF (tertile 1), the adjusted odds ratios for Ad36(+) were 2.2 (95% CI: 1.2-4.0), 2.4 (95% CI: 1.4-4.0), and 1.8 (95% CI: 1.0-3.3), respectively, for those in the highest concentrations of TNF-α, IL-6, and VEGF (tertile 3). No association was observed between Ad36(+) and fat mass. These data suggest that Ad36(+) is associated with biomarkers implicated in inflammation, but not with greater fat mass. The second study (Chapter 4) addressed relationships of Ad36(+), bone strength, assessed by peripheral quantitative computed tomography, and serum inflammatory-related markers in 78 obese females ages 9-12 years. After adjusting for age, race, fat mass, and FFST mass, Ad36(+) participants had lower radial strength-strain index (SSI) than Ad36-seronegative [Ad36(-)] participants (P=0.05). Ad36(+) participants had higher concentrations of TNF-α and VEGF versus Ad36(-) participants (both P<0.05). Radial SSI did not correlate with serum TNF-αand VEGF, suggesting that lower cortical bone strength is not attributed to higher concentrations of inflammatory-related markers observed in Ad36(+) obese females. This research supports associations of Ad36(+) with biomarkers implicated in inflammation and with cortical bone strength, but not with adiposity. Prospective studies are needed to determine the effects of Ad36(+) exposure in childhood on long-term health.