Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Harvard Medical School, Boston, MA 02215, USA.
Int J Mol Sci. 2021 Feb 1;22(3):1435. doi: 10.3390/ijms22031435.
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 γ (PPARγ) 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 PPARγ 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.
肺动脉高压（PH）与肥胖相关的代谢炎症有关，但脂肪组织在 PH 发病机制中的作用尚不清楚。我们假设在人类和实验性 PH 中，脂肪组织来源的代谢调节剂发生改变。我们测量了特发性 PH 患者和健康对照组循环中脂肪酸结合蛋白 4（FABP-4）、成纤维细胞生长因子 21（FGF-21）、脂联素的水平以及肺组织中 FABP-4、FGF-21 和过氧化物酶体增殖物激活受体γ（PPARγ）的 mRNA 水平。我们还评估了三种最常用的实验性肺动脉高压啮齿动物模型中这些介质在肺和脂肪组织中的表达。与对照组相比，PH 患者的循环 FABP-4、FGF-21 和脂联素水平显著升高，这些调节剂和 PPARγ 的 mRNA 水平在人类 PH 肺和实验性 PH 大鼠的肺中也显著升高。这些发现伴随着实验性 PH 中与葡萄糖摄取、糖酵解、三羧酸循环和脂肪酸氧化相关的脂肪组织基因的 mRNA 水平增加。我们的研究结果表明，人类 PH 中的代谢改变在疾病的啮齿动物模型中得到了重现，并提示脂肪组织可能有助于 PH 的发病机制。
