Severe pulmonary hypertension is associated with altered right ventricle metabolic substrate uptake

Am J Physiol Lung Cell Mol Physiol. 2015 Sep 1;309(5):L435-40. doi: 10.1152/ajplung.00169.2015. Epub 2015 Jun 26.


In severe pulmonary hypertension (SPH), prior studies have shown an increase in right ventricle (RV) uptake of glucose, but it is unclear whether there is a change in the relative utilization of fatty acids. We hypothesized that in the RV in SPH, as in left ventricular (LV) failure, there is altered substrate utilization, with increased glucose uptake and decreased fatty acid uptake. SPH was induced in rats by treatment with the VEGF receptor inhibitor SU5416 and 3 wk of hypoxia (10% FiO2 ), followed by an additional 4 wk of normoxia (SU-Hx group). Control rats were treated with carboxymethylcellulose vehicle and 7 wk of normoxia (CMC-Nx group). The rodents then underwent positron emission tomography with sequential administration of two radiotracers, 2-deoxy-2-[(18)F]fluoroglucose ((18)F-FDG) and 14-(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid ((18)F-FTHA), analogs of glucose and fatty acid, respectively. Five CMC-Nx and 3 SU-Hx rats completed the entire experimental protocol. In the RV, there was a mild increase in (18)F-FDG uptake (1.35-fold, P = 0.085) and a significant decrease in (18)F-FTHA uptake (-2.1-fold, P < 0.05) in the SU-Hx rats relative to the CMC-Nx rats. In the LV, SU-Hx rats had less uptake of both radiotracers compared with CMC-Nx rats. Less RV fatty acid uptake in SPH was corroborated by decreased fatty acid transporters and enzymes in the RV tissue, and specifically a decrease in lipoprotein lipase. In the RV in rats with SPH, there is a major shift in metabolic substrate preference, largely due to decreased fatty acid uptake.

Keywords: fatty acid oxidation; metabolism; pulmonary hypertension; right ventricle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Fatty Acid Transport Proteins / metabolism
  • Fatty Acids / metabolism*
  • Female
  • Glucose / metabolism*
  • Heart Ventricles / metabolism*
  • Heart Ventricles / physiopathology*
  • Hypertension, Pulmonary / physiopathology*
  • Hypoxia / physiopathology*
  • Indoles / pharmacology
  • Lipoprotein Lipase / metabolism
  • Oxidation-Reduction
  • Positron-Emission Tomography
  • Protein Kinase Inhibitors / pharmacology
  • Pyrroles / pharmacology
  • Radiopharmaceuticals
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors


  • Fatty Acid Transport Proteins
  • Fatty Acids
  • Indoles
  • Protein Kinase Inhibitors
  • Pyrroles
  • Radiopharmaceuticals
  • Semaxinib
  • Receptors, Vascular Endothelial Growth Factor
  • Lipoprotein Lipase
  • Glucose