ArticleObesity (Silver Spring, Md.)2026
Epigenetic Signature of the Metastable Epiallele VTRNA2-1: Adipose Dysfunction and Suboptimal Bariatric Outcomes.
Article in Obesity (Silver Spring, Md.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveVTRNA2-1 is a metastable epiallele whose methylation is associated with metabolic homeostasis via PKR-mediated inflammation and adipocyte function. We aimed to determine whether preoperative VTRNA2-1 promoter methylation in peripheral blood predicts long-term excess weight loss (%EWL) after bariatric surgery. We explored transcriptional signatures in adipose tissue to clarify the relationship between early-life epigenetic imprinting on adult metabolic plasticity and surgical outcomes in patients with severe obesity.
methodsIn the OCEAN prospective registry (2011-2024), 179 adults underwent bariatric surgery. Peripheral blood DNA VTRNA2-1 methylation was classified as hypo-, intermediate, or hyper-methylated. %EWL was recorded at 3, 6, 12, and 24 months. Adipose tissue was assayed for IL13, PRDM16, and related transcripts.
resultsVTRNA2-1 methylation showed a bimodal distribution, differing significantly from controls (p = 0.002). Hypermethylated patients had lower VTRNA2-1 expression (p < 0.001) and greater %EWL at 12 (67.8% ± 19.1% vs. 61.8% ± 17.5%; p = 0.047) and 24 months (68.7% ± 21.9% vs. 60.4% ± 19.3%; p = 0.040). The hypomethylated group maintained a stable weight loss plateau between 12 and 24 months. Hypomethylation was associated with nominally higher IL13 and PRDM16 mRNA in adipose tissue (exploratory; uncorrected p < 0.05).
conclusionsVTRNA2-1 methylation status is associated with predictable variations and offers potential for preoperative risk stratification and personalized therapeutic strategies in managing severe obesity.
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