Pulmonary hypertension patients showed significantly increased adipose tissue deposition in the pericardial region, visceral organs, and skeletal muscles compared with healthy controls.
Case-Control
Are there differences in fat distribution patterns and inflammatory molecular pathways between patients with pulmonary hypertension and healthy controls?
Pulmonary hypertension is associated with increased pericardial and intramuscular adiposity and systemic pro-inflammatory molecular signatures, suggesting potential new targets for metabolic or anti-inflammatory interventions.
Abstract Rationale Obesity is frequently observed among patients with pulmonary hypertension (PH), yet evidence regarding its association with PH outcomes remains conflicting, leading to ongoing debate over the “obesity paradox.” Beyond total adiposity, fat distribution patterns represent an underexplored dimension of PH pathogenesis. Intramuscular fat accumulation, increasingly recognized in aging, metabolic disorders, and inflammatory diseases, may further contribute to muscle dysfunction and exercise intolerance in PH. To address these gaps, this study aims to characterize fat distribution patterns and related molecular pathway regulation in human cohorts. Methods We identified PH patients and healthy controls from the UK Biobank using a combination of ICD-9/ICD-10 and OPCS codes. Fat distribution and tissue mass differences were assessed using MRI and DEXA imaging data. Blood biochemical marker analysis and unbiased plasma proteomic profiling using Olink, followed by pathway enrichment analyses, were performed to identify associated biomarkers and molecular pathways. Results Compared with controls, PH patients demonstrated higher BMI and lower baseline physical activity. After adjustment for baseline characteristics including BMI, PH patients showed significantly increased adipose tissue deposition in the pericardial region, visceral organs, and skeletal muscles of all four extremities (Figure 1). Both total and fat-free lean mass of the arms and legs were elevated in PH patients, while cardiac function and bone density remained similar between two groups. Among 30 blood biochemical markers analyzed, fat deposition was positively associated with C-reactive protein and rheumatoid factor, and negatively associated with testosterone and aspartate aminotransferase levels. Proteomic and pathway enrichment analyses revealed positive associations between fat deposition and pro-inflammatory pathways such as inflammatory response, neutrophil degranulation, and chemokine-mediated signaling. In contrast, lean mass showed negative associations with these inflammatory pathways. Conclusions These findings support that PH is characterized by systemic metabolic dysregulation and inflammation-associated alterations in fat distribution. Increased pericardial and intramuscular adiposity may represent pathophysiologic signatures contributing to cardiometabolic burden in PH, while increased lean mass may reflect compensatory remodeling that mitigates inflammation. Together, these findings highlight distinct fat distribution patterns and molecular signatures in PH that may inform mechanistic understanding and identify new targets for metabolic or anti-inflammatory interventions. This abstract is funded by: None
Meng et al. (Fri,) conducted a case-control in Pulmonary Hypertension. Pulmonary hypertension (exposure) vs. Healthy controls was evaluated on Fat distribution and tissue mass differences. Pulmonary hypertension patients showed significantly increased adipose tissue deposition in the pericardial region, visceral organs, and skeletal muscles compared with healthy controls.