1126-OR: MALAT1 Is an Exercise-Responsive Regulatory RNA Associated with Metabolic Traits

Introduction and Objective: Chronic inflammation contributes to insulin resistance and type 2 diabetes, yet regulatory RNAs linking metabolic disease to modifiable lifestyle factors remain poorly understood. The long non-coding RNA MALAT1 regulates transcriptional and inflammatory signaling, but its role in metabolic health and exercise responsiveness has not been fully characterized. Methods: We analyzed MALAT1 across Latino biobank datasets, human tissues, and exercise interventions using multiomics approaches. Whole-blood transcriptomic data from Latino adults in the AIR registry (n=184) were analyzed to assess associations between MALAT1 gene expression and metabolic traits. MALAT1 expression was evaluated in human skeletal muscle following acute exercise, and skeletal muscle DNA methylation was assessed after 8 weeks of exercise training. MALAT1 genetic variants were examined for associations with metabolic traits in El Banco por Salud (n=1,026). Results: In whole blood, MALAT1 expression was associated with lipid, glycemic, blood pressure, and insulin resistance traits, with small to modest correlations (r ≈ -0.16 to 0.30, P<0.05). In skeletal muscle, MALAT1 expression increased ~2.7-fold 30 minutes after acute exercise (P<0.05) and showed increased DNA methylation after 8-weeks of training (14.2% to 16.5%, P<0.05). In El Banco por Salud, multiple SNPs were associated with metabolic traits. Notably, rs11227275 was associated with higher ALT and a more atherogenic lipid profile, including increased cholesterol, LDL/HDL ratio, triglycerides, and VLDL (all P<0.05). In contrast, a large-correlated SNP block showed protective associations, including lower ALT and improved glycemic traits (all P<0.05). Conclusion: MALAT1 is an exercise-responsive lncRNA associated with adverse and protective metabolic phenotypes across expression, epigenetic, and genetic analyses. These findings support MALAT1 as a candidate molecular link between metabolic disease, inflammation, and exercise adaptation, with relevance to T2D risk and prevention.