Obesity is an important disease in some regions, such as the Xinjiang region, China. It directly and indirectly increases the likelihoods of various diseases [2–4, 16, 17]. Thus it is of great importance to identify the related factors of obesity and to investigate the underlying mechanisms. It is found that human Ad36 increases adiposity in several animal models, including rodents and non-human primates [18, 19]. Since Ad36 is associated with human obesity, it is important to determine the relationship between its infection and obesity [20, 21]. In this study, the relationship between Ad36 infection and obesity and the underlying mechanism of Ad36 in obesity was investigated.
Our results showed that, in the obese group, the serum levels of TG, adiponectin and visfatin were found to be significantly different between the obese individuals infected with Ad36 or not. The TG levels in Ad36-infected obese subgroup were decreased, while serum levels of adiponectin and visfatin in Ad36-infected obese subgroup were increased. The results suggest that in the obese individuals infected with Ad36, the expression of adiponectin in serum was elevated and thus TG levels were improved. Previous studies have shown that Ad-36 infection is associated with reductions in serum TC and TG both in adults and children [14, 22]. Thus, our data in obese patients from Xinjiang region were consistent with previous reports. And, our data further confirmed that Ad36 was related with obesity, suggesting that Ad36 might be involved in the etiology of obesity.
Studies have shown that inflammation contributes to the maintenance of the obesity state and that Ad36 may maintain the obesity state by inducing inflammation [23–25]. Adipose tissue in obese subjects is characterized by macrophage infiltration . Thus, to determine whether Ad36 induces macrophage infiltration in adipose tissue, we detected the expression of CD68 in both abdominal subcutaneous and omental adipose tissues by immunohistochemistry. The expression of CD68 is indicative of macrophage infiltration. The results showed that, in the individuals with Ad36 infection, the macrophage infiltration in the obese group was also significantly higher than that in the non-obese group in both abdominal subcutaneous and omental adipose tissues. Our results, which were consistent with previous reports, indicate that macrophage infiltration may be involved in Ad36 induced obesity.
Ad36 infection accelerates the differentiation of preadipocytes to adipocytes in 3T3-L1 cells and human preadipocytes [13, 27]. Although Ad36 E4orf1 gene is thought to be involved in the mechanism underlying virus-induced obesity, other related molecular factors are undetermined. As previously reported [5–10], adiponectin and visfatin are two important factors involved in obesity. Our results showed that serum levels of adiponectin and visfatin were significantly increased in obese patients infected with Ad36. Thus, to investigate whether adiponectin and visfatin are involved in Ad36-induced obesity, real-time PCR was performed to determine expression levels of APMI and Visfatin genes in the 3T3-L1 preadipocytes infected with Ad36. The expression of Ad-36 E4orf1 gene was increased, indicating that the 3T3-L1 preadipocytes were infected with Ad36. Infection of 3T3-L1 cells with Ad36 suggested that APMI mRNA levels and Visfatin mRNA levels were increased from the day 3 and day 4 post-infection, respectively. These results indicate that infection of preadipocytes with Ad36 increases gene expression of APMI and Visfatin genes, and further suggest that APMI and Visfatin genes may be involved in the mechanism underlying the effect of Ad36 infection on the obese patients. The mechanisms underlying the effect of Ad36 infection will be further investigated in the future.
In summary, our data showed that Ad36 was associated with obesity of patients from Xinjiang region. And, Ad36 infection may be a factor related with macrophage infiltration in adipose tissues of the obese patients. In addition, increased levels of adiponectin and visfatin might be the mechanisms underlying the effect of Ad36 infection on obesity.