Roles of Lipid Metabolism in Pulmonary Hypertension: Friend or Foe?

Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder characterized by vascular remodeling and right ventricular (RV) failure. Recently, attention to lipid metabolism in PH has revealed multiple mechanisms that drive disease progression, including alterations in energy supply, oxidative stress, inflammatory signaling, and epigenetic regulation. Notably, lipid metabolism in PH exhibits marked spatiotemporal heterogeneity. This creates a therapeutic paradox in which the same metabolic intervention may exert opposing effects depending on tissue type and disease stage. Despite these challenges, targeting lipid metabolism remains an attractive therapeutic strategy. Preclinical and early clinical studies suggest that both small-molecule metabolic modulators and natural compounds hold promise for reversing pulmonary vascular remodeling and improving RV function. This review summarizes current advances in lipid metabolic reprogramming in PH and highlights the challenges of developing tissue- and time-specific interventions.