Discussion
These findings suggest that obesity impairs lung vascular and alveolar regeneration and adiponectin is one of the key factors to improve lung regeneration in obese people.
Methods
Unilateral PNX is performed on Lep o b / o b obese mice to examine vascular and alveolar regeneration.
Results
Regenerative lung growth and expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR2 induced after PNX are inhibited in Lep o b / o b obese mice. The levels of adiponectin that exhibits pro-angiogenic and vascular protective properties increase after unilateral PNX, while the effects are attenuated in Lep o b / o b obese mice. Post-PNX regenerative lung growth and increases in the levels of VEGF and VEGFR2 are inhibited in adiponectin knockout mice. Adiponectin stimulates angiogenic activities in human lung endothelial cells (ECs), which is inhibited by decreasing the levels of transcription factor Twist1. Adiponectin agonist, AdipoRon restores post-PNX lung growth and vascular and alveolar regeneration in Lep o b / o b obese mice.