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

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Manriquez, Victor ; Brito, Roberto ; Pavez, Monica ; Sapunar, Jorge ; Fonseca, Luis ; Molina, Victor ; Ortiz, Eugenia ; Baeza, Romilio ; Reimer, Camila ; Charles, Maria ; Schneider, Constance ; Hirata, Mario Hiroyuki ; Hirata, Rosario Dominguez Crespo ; Cerda, Alvaro

• Document type: Journal article
• Source: International Journal of Obesity; v. 48, n. 10, p. 7-pg., 2024-06-19.

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 PPAR gamma 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. (AU)

• FAPESP's process: 22/09576-1 - Integrative study of non-coding RNAs and metabolome profile in obese patients: pathophysiology mechanism contribution to search druggable targets
• Grantee: Mario Hiroyuki Hirata
• Support Opportunities: Regular Research Grants