Adipokines and Metabolic Regulators in Human and Experimental Pulmonary Arterial Hypertension

Pulmonary hypertension (PH) is associated with meta-inflammation related to obesity but the role of adipose tissue in PH pathogenesis is unknown. We hypothesized that adipose tissue-derived metabolic regulators are altered in human and experimental PH. We measured circulating levels of fatty acid binding protein 4 (FABP-4), fibroblast growth factor -21 (FGF-21), adiponectin, and the mRNA levels of FABP-4, FGF-21, and peroxisome proliferator-activated receptor gamma (PPAR gamma) in lung tissue of patients with idiopathic PH and healthy controls. We also evaluated lung and adipose tissue expression of these mediators in the three most commonly used experimental rodent models of pulmonary hypertension. Circulating levels of FABP-4, FGF-21, and adiponectin were significantly elevated in PH patients compared to controls and the mRNA levels of these regulators and PPAR gamma were also significantly increased in human PH lungs and in the lungs of rats with experimental PH compared to controls. These findings were coupled with increased levels of adipose tissue mRNA of genes related to glucose uptake, glycolysis, tricarboxylic acid cycle, and fatty acid oxidation in experimental PH. Our results support that metabolic alterations in human PH are recapitulated in rodent models of the disease and suggest that adipose tissue may contribute to PH pathogenesis.

Automated summary

The study found significantly elevated levels of fatty acid binding protein 4, fibroblast growth factor-21, and adiponectin in the circulation of pulmonary hypertension patients, with increased mRNA levels of these metabolic regulators and PPAR γ gene in patient lung tissue. Experimental rodent models of PH and human patients demonstrated increased gene expression related to glucose uptake, glycolysis, tricarboxylic acid cycle, and fatty acid oxidation.