New wine into old wineskins: PGC-1α and NF-κB in obesity and acute pancreatitis

Obesity and acute pancreatitis are both proinflammatory conditions. Importantly, obesity increases severity in acute pancreatitis by enhancing inflammation. In a recent issue of The Journal of Pathology, Pérez and Ruiz-Pérez et al connected obesity and pancreatitis for the first time, through the transcriptional regulator PPARγ coactivator 1α (PGC-1α). Obesity reduces pancreatic PGC-1α levels and potentiates not only oxidative but also IL-6-mediated inflammatory damage during acute pancreatitis by relieving the binding of PGC-1α to the NF-κB subunit p65. Blockade of the IL-6 receptor subunit gp130 ameliorated tissue injury, substantiating the importance of deregulated PGC-1α/p65/IL-6 signaling in obesity and acute pancreatitis.