Obesity (Silver Spring, Md.) · 2026
Epigenetic Signature of the Metastable Epiallele VTRNA2-1: Adipose Dysfunction and Suboptimal Bariatric Outcomes.
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Huang Yi-Chun, Hou Kuan-Jung, Tsai Ming-Lung, Liu Keng-Hao, Ho Ming-Yun, Yeh Jih-Kai, Chen Chun-Chi, Chia Chin-Yuan, Fan Wen-Lang, Hsieh I-Chang, Ye Ta-Sen, Wang Horng-Dar, Tsai Chi-Neu, Wang Chao-Yung
Аннотация
OBJECTIVE: VTRNA2-1 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.
METHODS: In 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.
RESULTS: VTRNA2-1 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).
CONCLUSIONS: VTRNA2-1 methylation status is associated with predictable variations and offers potential for preoperative risk stratification and personalized therapeutic strategies in managing severe obesity.
METHODS: In 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.
RESULTS: VTRNA2-1 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).
CONCLUSIONS: VTRNA2-1 methylation status is associated with predictable variations and offers potential for preoperative risk stratification and personalized therapeutic strategies in managing severe obesity.