SLC16A1 lactylation links epimetabolic reprogramming of triglycerides (50:3 and 50:1) to blood pressure regulation

Objective This study aims to investigate the causal relationship between SLC16A1 lactylation modification and systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as the potential mediating role of lipidomics-triglyceride (50:3/50:1) in this association. Methods This study combines eQTL data and lactylation modifications to identify 16 associated genes, using Mendelian randomisation (MR) to assess their effects on SBP and DBP. It also employs summary-data-based Mendelian randomisation (SMR) for validation and lipidomics analysis to explore the effect of SLC16A1 lactylation on triglyceride (TG) subtypes (50:3/50:1). Finally, mediation analysis quantifies the role of triglyceride subtypes in the link between SLC16A1 lactylation and blood pressure changes. Results SLC16A1 lactylation modification negatively correlates with SBP ( β = -1.181, P < 0.001) and DBP ( β = -0.9954, P < 0.001), confirmed by SMR analysis ( P < 0.001). Lipidomics shows TG(50:3) and TG(50:1) are crucial for SBP and DBP, with TG(50:3) mediating 11.32% of the effect on SBP ( P = 0.0381) and TG(50:1) mediating 9.32% on DBP ( P = 0.00066). Conclusion This study reveals that SLC16A1 lactylation modification might regulate SBP and DBP by suppressing the levels of TG(50:3) and TG(50:1), offering potential therapeutic targets for precision interventions in metabolic hypertension.