Novel short-term effects of adenovirus Ad-36 on hamster lipoproteins

Abstract

OBJECTIVE: Human adenovirus Ad-36 induces adiposity and lowers total serum cholesterol in chickens, mice and marmosets and Ad-36 antibodies are associated with human obesity. We examined the early effects of Ad-36 inoculation on plasma cholesterol levels in hamsters fed a hyperlipidemic diet. DESIGN: A total of 32 male Golden Syrian hamsters were divided into two equal weight-matched groups and intranasally inoculated with Ad-36 (INF: infected) or media (CON: control). In each group, the animals were fed either a purified diet (PF, n ¼ 8) 40%en fat 7194 mg cholesterol/1000 kcal or chow (C, n ¼ 8) ad libitum. Animals were killed 5 weeks postinoculation. RESULTS: Nested PCR assay detected Ad-36 DNA in the lung, liver, visceral adipose tissue and skeletal muscle of the INF group, but not in the CON animals. Ad-36 antibodies were detected in the INF group only. For all animals, total plasma cholesterol (TC) was not significantly affected by Ad-36 treatment (203792 vs 193775 mg/dl, P ¼ NS; INF vs CON, respectively). In 5 weeks, Ad-36 infection had no effect on TC concentration in hamsters fed chow (128739 vs 130727 mg/dl, INF-C vs CON-C, respectively) or those fed PF (269770 vs 256747 mg/dl, INF-P vs CON-P, respectively). However, lipoproteins isolated by density gradient ultracentrifugation showed a greater proportion of LDL cholesterol in INF animals, as compared to CON (28.471.6% vs 16.471.2%, P ¼ 0.02), regardless of dietary treatment (INF-P vs CON-P: 27.372.1 vs 15.771.5%, P ¼ 0.07; and INF-C vs CON-C: 29.471.2 vs 17.071.1%, P ¼ 0.009). This shift appears to be from HDL cholesterol to the LDL fractions. CONCLUSION: These data suggest that in the hamster (a model resembling several aspects of human lipoprotein metabolism), Ad-36 infection may acutely affect the intravascular processing of lipoproteins resulting in a more atherogenic lipoprotein profile.

Adenovirus 36 infection and obesity

“…The animals also had low serum TC and TG levels Pasarica et al 14 In rats infected with AD-36, increase in body weight, in insulin sensitivity and glucose uptake were observed Dhurandhar et al 15 A significant longitudinal association between positive antibody status and weight gain and decreased TC levels was found during the 18 months after the appearance of viral antibodies in 15 male rhesus monkeys. Moreover, 28 weeks after inoculation, three male marmosets inoculated with AD-36 showed a threefold gain in body weight, greater fat gain, and lower serum cholesterol levels in relation to baseline (p < 0.05) than three uninfected controls Kapila et al 16 AD-36 infection is associated with a decrease in TC levels in hamsters, and may occur simultaneously with a shift from high-density lipoprotein to low-density lipoprotein cholesterol Dhurandhar et al 17 AD-36 infection can be transmitted horizontally from one infected chicken to another chicken sharing the same cage. Additionally, the transfusion of a small amount of blood from AD-36 infected animals in uninfected animals successfully transmitted infection, and the recipients subsequently became obese Pasarica et al 18 Norepinephrine levels in the paraventricular nucleus of the brain are significantly lower in AD-36 infected rats than in healthy controls.…”

“…15 The results of a study of hamsters confirmed that AD-36 infection is associated with decreased TC levels, but also indicated that this could occur at the same time as a shift from high-density lipoprotein to low-density lipoprotein cholesterol. 16 This may be a related deleterious event that could further increase the negative effect of AD-36 infection on body weight, thus increasing the risk of cardiovascular disorders.…”

Adenovirus-36 Seropositivity and Its Relation with Obesity and Metabolic Profile in Children

“…The explanation for this association is unknown. Some evidence from animal studies showed in golden Syrian hamsters that the cholesterol-lowering effect of Ad-36 infection is associated with a shift in plasma cholesterol from high-density lipoprotein to low-density lipoprotein cholesterol [22]. Another study, in wild-type (WT) mice and monocyte chemoattractant protein-1 knockout mice that were infected with Ad-36, found that Ad-36 infected WT mice increased insulin sensitivity, and lipid parameters such as HDL-c, LDL-c, and total cholesterol concentrations were lower than in mock-infected WT mice.…”

Adipogenic Cascade Can Be Induced Without Adipogenic Media by a Human Adenovirus

“…Human Adenovirus Ad36 is such an adipogenic agent, which increases adiposity in experimentally infected animal models such as chickens, mice, rats, and marmosets (5)(6)(7)(8)(9); increases commitment, differentiation, and lipid accumulation in adipocyte progenitors (10,11); and improves glucose disposal in cell culture and animal models (9,(12)(13)(14). In the United States, Ad36 shows about 15-17% prevalence in adult population (15).…”