APLN and Cowden disease: Apelin is highly produced in the adipose tissue of patients with CD compared with that from controls, and the systemic delivery of apelin significantly ameliorates the disease activity index and colitis scores in IL-10-deficient mice by downregulating inflammatory cytokines such as TNF-α and IL-6, suggesting that apelin is a key mediator and a therapeutic target of immune-mediated injury [119].