Adenovirus 36 seropositivity is related to the expression of anti-adipogenic lncRNAs GAS5 and MEG3 in adipose tissue obtained from subjects with obesity.

BACKGROUND: Human Adenovirus D-36 (HAdV-D36) promotes adipogenesis in cellular and animal models and may contribute to the development of human obesity. Induction of PPARγ by HAdV-D36 seems to have a central role in the maintenance of adipogenic status. There is limited information about epigenetic mechanisms contributing to this process in human adipose tissue. This study evaluated the expression of lncRNAs (ADINR, GAS5 and MEG3) and miRNAs (miR-18a and miR-140) involved in the adipogenic process in visceral adipose tissue (VAT) of subjects with obesity with previous HAdV-D36 infection (seropositive) and unexposed (seronegative) subjects with obesity. METHODS: Individuals with obesity were grouped according to the presence of antibodies against HAdV-D36 (Seropositive: HAdV-D36[+], n = 29; and Seronegative: HAdV-D36[-], n = 28). Additionally, a group of individuals without obesity (n = 17) was selected as a control group. The HAdV-D36 serology was carried out by ELISA. Biopsies of VAT were obtained during an elective and clinically indicated surgery (bariatric or cholecystectomy). RNA extraction from VAT was performed and the expression of PPARG and non-coding RNAs was evaluated by qPCR. RESULTS: HAdV-D36[+] individuals had lower expression of anti-adipogenic lncRNAs GAS5 (p = 0.016) and MEG3 (p = 0.035) compared with HAdV-D36[-] subjects with obesity. HAdV-D36[+] subjects also presented increased expression of the adipogenic miRNA miR-18a (p = 0.042), which has been reported to be modulated by GAS5 through a RNA sponging mechanism during adipogenic differentiation. Additionally, an inverse correlation of GAS5 with PPARG expression was observed (r = -0.917, p = 0.01). CONCLUSION: Our results suggest that HAdV-D36 is related to non-coding RNAs implicated in adipogenesis, representing a potential mechanism by which previous HAdV-D36 infection could be associated with the long-term maintenance of adipogenic status, probably through the GAS5/miR-18a axis.

Influence of adenovirus 36 seropositivity on the expression of adipogenic microRNAs in obese subjects.

BACKGROUND: Infection by Adenovirus 36 (Ad-36) has been associated with adipogenesis using cell and animal models, and a high risk of developing obesity has been reported in Ad-36-seropositive individuals. However, molecular mechanisms involved in the maintenance over the years of adipogenesis associated with Ad-36 has not been investigated in human adipose tissue. Epigenetic mechanisms, such as micro-RNAs (miRNAs) that regulate gene expression at the post-transcriptional level, have shown an important role in the development and maintenance of metabolic diseases. AIM: This study investigated the expression of miRNA associated with the adipogenic process in visceral adipose tissue from obese individuals according to Ad-36 serology. METHODS: Obese individuals were separated according to their status of Ad-36 serology in seropositive (Ad-36 (+); n = 29) and seronegative (Ad-36 (-); n = 28) groups. Additionally, a group of lean controls (n = 17) was selected to compare with obese individuals. Biopsies of visceral adipose tissue were obtained to evaluate miRNA and gene expression. The study of Ad-36 serology was carried out by ELISA. The expression of pro-adipogenic (miR-17 and miR-210) and anti-adipogenic (miR-155, miR-130 and miR-27a) miRNAs was evaluated using Taqman advanced miRNA assays by qPCR. The expression of adipogenes encoding LEP, ADIPOQ, and PPARγ was evaluated by Taqman predesigned assays through qPCR. RESULTS: The obese group had higher LEP (p < 0.001) and PPARγ (p = 0.016) expression and lower ADIPOQ expression (p = 0.017), and also had higher expression of miR-210 (p = 0.039), whereas lower expression of miR-155 (p = 0.019) and miR-27a (p = 0.028) as compared to lean controls. Higher PPARγ expression (p = 0.008), but no influence on LEP or ADIPOQ expression was observed in Ad-36 (+) group. Those seropositive individuals also had higher expression of the miR-17 (p = 0.028) and lower levels of miR-155 (p = 0.031) in adipose tissue as compared to seronegative subjects. CONCLUSIONS: Individuals with previous infection by Ad-36 had higher expression of the pro-adipogenic miR-17 and lower expression of the anti-adipogenic miR-155, which could lead to an increased adipogenic status by positively modulating PPARγ expression in adipose tissue from obese subjects.

Adenovirus 36 seropositivity is related to obesity risk, glycemic control, and leptin levels in Chilean subjects.

BACKGROUND: Adenovirus 36 (Ad-36) has been associated to adiposity in animal and in vitro studies. Ad-36 seropositivity has also been reported to contribute to obesity risk in children and adult populations. We investigated the relationship of Ad-36 serology with obesity and metabolic parameters in a Chilean population. SUBJECTS AND METHODS: Clinical and anthropometric data were obtained and blood samples were drawn from 99 lean (BMI: 18.5-24.9 kg/m2) and 151 obese (BMI > 30 kg/m2) subjects. Laboratory tests included lipid profile as well as glucose, insulin, leptin, and adiponectin levels. Ad-36 seropositivity was evaluated in serum samples by enzyme-linked immunosorbent assay. RESULTS: Seroprevalence of Ad-36 was higher in the obese group (58%) than in lean controls (34%) demonstrating that individuals previously infected with Ad-36 have higher risk of obesity in the study population (OR: 2.67, 95%CI: 1.58-4.51, p < 0.001). Interestingly, Ad-36 was related to lower concentrations of triglycerides and VLDL cholesterol in lean subjects (p = 0.049) and lower leptin in obese individuals (p = 0.014). Previous Ad-36 infection was also related to lower glycemia, insulinemia, and HOMA-IR (p < 0.05) in obese subjects who were not under antidiabetic drugs. CONCLUSIONS: Our results provide evidence of the contribution of previous Ad-36 infection to an increased risk of obesity in adult Chilean population. Ad-36 seropositivity was also associated to lipid profile, glycemic control, and leptin levels in adult Chilean population.