Strength training induces ABHD5-ATGL axis to counteract mesenteric fat accumulation in obese Swiss mice

Adipose tissue plays a central role in systemic metabolic regulation, and impairments in lipid turnover are a hallmark of obesity associated adipose dysfunction. Lipolytic activation depends on perilipin-1 (PLIN1) phosphorylation, which enables the release of α/β-hydrolase domain-containing-5 (ABHD5), a key co-activator of adipose triglyceride lipase (ATGL). Obesity disrupts this regulatory axis, reducing ABHD5 expression and favoring a lipogenic and monounsaturated fatty acid (MUFA) enriched environment driven in part by increased stearoyl-CoA desaturase-1 (SCD1). These contribute to adipocyte hypertrophy, impaired lipid mobilization, and dysfunctional extracellular matrix. This study investigated whether a brief strength training protocol following fourteen weeks of induction on a high-fat diet containing 35% fat could restore the lipolytic machinery and rebalance lipid metabolism in the mesenteric adipose tissue of obese Swiss mice. Seven days of strength training at 70% of loading capacity increased ABHD5 gene expression (p = 0,0012) and protein content (p = 0,0003), accompanied by elevations in pHSL and pPLIN1 (p = 0,0062 and p = 0,0002), indicating lipolytic activation. Exercise reduced mass and adipocyte size, and demonstrated that obesity increased MUFA abundance (p = 0,0039). Correlation revealed that SCD1 showed a positive association with sedentarism, these gene as central determinant of lipid composition in mesenteric adipose tissue. Additionally, strength training decreases MMP2 and increases MMP9 activity (p = 0,002 and p = 0,0001), a pattern consistent with adaptive structural reorganization rather than fibrotic progression. Collectively, these findings indicate that short-term strength training is a non-pharmacological strategy to counteract mesenteric adipose dysfunction by restoring lipolytic balance and improving lipid metabolic profiles before mass loss and changes in eating behavior occur.