Seven days of strength training reprogram the hydroxymethylation in visceral adipose tissue of obese Swiss mice.

Abstract

Excessive accumulation of visceral adipose tissue induced by a high-fat diet promotes epigenetic modifications in DNA, increasing Nfkb transcription and pro-inflammatory cytokine synthesis. This study evaluated the epigenetic effects of obesity and seven days of strength exercise on DNA demethylation in the Nfkb transcription region. Swiss mice were divided into three groups: lean controls (CT = 6), obese sedentary (OB = 6), and obese strength training (OBexT = 6). OB and OBexT received a high-fat diet (59% lipids) for fourteen weeks; OBexT performed daily climbing sessions for seven days. OB animals showed higher pro-inflammatory cytokine expression and NFKB protein content in mesenteric adipose (mean ± SD: OB = 4.35 ± 3.37; OBexT = 0.59 ± 0.28; CT = 1.00 ± 0.70), with significant reduction after training (p < 0.05; η2 = 0.502). Pairwise comparison revealed a large effect size between OB and OBexT (d = 1.57). Demethylation in adipose tissue was elevated in OB mice, increasing gene availability and Nfkb transcription (OB = 4.01 ± 1.23; OBexT = 1.70 ± 1.06; CT = 0.99 ± 0.22), with a strong reduction post-exercise (p < 0.01; η2 = 0.6546; d = 2.01). This reduction limited gene accessibility for Nfkbp65 phosphorylation, highlighting epigenetic modulation. These results demonstrate, for the first time, that only seven sessions of strength training can reprogram epigenetic marks in mesenteric adipose tissue, attenuating transcription of inflammatory mediators during an obesogenic state. Collectively, our findings support strength training as an effective short-term epigenetic regulator of inflammatory gene expression in adipose tissue.