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Genetics and Epigenetics

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

Abstract

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.

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Fig. 1: Expression of lncRNAs in visceral adipose tissue from subjects with and without obesity.
Fig. 2: Expression of lncRNAs in visceral adipose tissue from subjects with obesity according to HAdV-D36 serology.
Fig. 3: Expression of miR-18a and miR-140 in visceral adipose tissue from subjects with and without obesity.
Fig. 4: Expression of miRNAs in visceral adipose tissue from subjects with obesity according to HAdV-D36 serology.
Fig. 5: The anti-adipogenic lncRNA GAS5 is negatively correlated with the expression of the mammalian adipogenesis master control gene PPARG.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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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 (CTO) 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. We gratefully acknowledge Sophie Baggett for her valuable assistance with grammatical revisions. This research was funded by FONDECYT (grant number 11150445) and by Joint Proposals University of La Frontera and São Paulo Research Foundation (UFRO-Chile/FAPESP-Brazil #FPP22-0025 and #2022/09576-1). VM and RBrito are recipients of fellowships from the National Agency for Research and Development (ANID-Chile).

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VM: Experimental procedures, data analysis and interpretation, writing the manuscript; RBrito: Experimental procedures and data analysis; MP, JS, MHH and RDCH: Conceptualization and study design, critical review of the manuscript; LF, VM, EO and RBaeza: Patient selection, clinical evaluation, obtention of biological samples; CR, MC and CS: Patient selection, clinical evaluation, recording of clinical and laboratory data; AC: Conceptualization and Study design, data analysis and interpretation, writing and critical review of the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Alvaro Cerda.

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Manríquez, V., Brito, R., Pavez, M. et al. Adenovirus 36 seropositivity is related to the expression of anti-adipogenic lncRNAs GAS5 and MEG3 in adipose tissue obtained from subjects with obesity. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01555-x

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