Decreases in adiponectin mediate inhibition of regenerative lung growth in obese mice

Obesity is associated with impairments of wound healing and tissue regeneration. Angiogenesis, the formation of new blood capillaries, plays a key role in organ regeneration and repair. Inhibition of lung angiogenesis impairs regenerative lung growth after unilateral pneumonectomy (PNX). However, the effects of obesity on post-PNX lung vascular and alveolar morphogenesis remain unclear. In this report, we have demonstrated that regenerative lung growth and angiogenic factor VEGFA expression induced by PNX are inhibited in Lepob/ob obese mice compared to Lepob/- mice. The levels of adiponectin, one of the adipokines that exhibits pro-angiogenic and vascular protective properties, increase in endothelial cells (ECs) isolated from remaining mouse lungs after unilateral PNX, while these effects are attenuated in Lepob/ob obese mice. Post-PNX lung growth, vascular and alveolar morphogenesis, and VEGFA levels in the lungs are inhibited in adiponectin knockout mice. Adiponectin agonist, AdipoRon stimulates post-PNX lung growth and vascular and alveolar morphogenesis in Lepob/ob obese mice. These findings suggest that obesity impairs lung vascular and alveolar regeneration and adiponectin may be one of the key molecules to improve lung regeneration in obese people.