APLN and obesity due to melanocortin 4 receptor deficiency: The opposing effects of apelin/ACE2 and angiotensin II have been shown in health and diseases such as heart failure, atherosclerosis and obesity/diabetes (Ashley et al., 2006; Gurzu et al., 2006; Iwanaga et al., 2006; Zhong et al., 2007; Chun et al., 2008; Barnes et al., 2013; Siddiquee et al., 2013) (Figure 9).