Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury.
Adiponectin (APN), an adipocyte-derived adipokine, has been shown to limit lung injury originating from endothelial cell (EC) damage. Previously we reported that obese mice with low circulatory APN levels exhibited pulmonary vascular endothelial dysfunction. This study was designed to investigate the cellular and molecular mechanisms underlying the pulmonary endothelium-dependent protective effects of APN. Our results demonstrated that in APN-/- mice, there was an inherent state of endothelium mitochondrial dysfunction that could contribute to endothelial activation and increased susceptibility to LPS-induced acute lung injury (ALI). We noted that APN-/- mice showed decreased expression of mitochondrial biogenesis regulatory protein peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and its downstream proteins nuclear respiratory factor 1, transcription factor A, mitochondrial, and Sirtuin (Sirt)3 and Sirt1 expression in whole lungs and in freshly isolated lung ECs from these mice at baseline and subjected to LPS-induced ALI. We further showed that treating APN-/- mice with PGC-1α activator pyrroloquinoline quinone enhances mitochondrial biogenesis and function in lung endothelium and attenuation of ALI. These results suggest that the pulmonary endothelium-protective properties of APN are mediated, at least in part, by an enhancement of mitochondrial biogenesis through a mechanism involving PGC-1α activation.-Shah, D., Torres, C., Bhandari, V. Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury.
['Shah|Dilip|D|', 'Torres|Claudio|C|', 'Bhandari|Vineet|V|']
D052242:Adiponectin D000818:Animals D004730:Endothelium, Vascular D058847:Inflammasomes D008070:Lipopolysaccharides D055370:Lung Injury D008297:Male D008661:Metabolism, Inborn Errors D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D008820:Mice, Obese D008928:Mitochondria D000071199:NLR Family, Pyrin Domain-Containing 3 Protein D001678:Organelle Biogenesis D057772:Vascular System Injuries
adipokine endothelial dysfunction acute lung injury PGC-1α mitochondria biogenesis