LEP and obesity due to melanocortin 4 receptor deficiency: An increase in the circulating leptin concentration has been observed in PDAC patients274 and is associated with increased PDAC risk in men.275 Interestingly, a recent study indicated that YAP/TAZ–TEAD stimulates leptin expression by directly interacting with an upstream enhancer site of the leptin gene.276 Bioactive peptides produced by neuronal and gastrointestinal (GI) cells (the brain‒gut axis) are also implicated in obesity-associated PDAC development.