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Genetics and Epigenetics

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

Abstract

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.

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Fig. 1: Influence of obesity and Ad-36 serology on the expression of LEP, ADIPOQ, and PPARG.
Fig. 2: Expression of miRNAs in visceral adipose tissue from non-obese and obese subjects.
Fig. 3: Influence of Ad-36 serology on the expression of miRNAs in visceral adipose tissue from obese subjects.

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Acknowledgements

We thank the volunteers for their participation in this research. We also thank physicians, nurses, and administrative staff from the Centro de Tratamiento de la Obesidad and the Laboratorio Clínico of the Clínica Alemana de Temuco. We thank Dr. Soledad Reyes and Lilian Saravia for the support in obtaining biological samples. This research was funded by FONDECYT-Chile (grant number 11150445) and CONICYT-Chile (grant number REDI170632).

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Manríquez, V., Gutierrez, A., Morales, A. et al. Influence of adenovirus 36 seropositivity on the expression of adipogenic microRNAs in obese subjects. Int J Obes 44, 2303–2312 (2020). https://doi.org/10.1038/s41366-020-00654-9

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