ACE and obesity due to melanocortin 4 receptor deficiency: Although different research indicated that the benefits induced by APT is associated with the upregulation of ACE2/Ang 1-7/Mas axis [26, 33], it is also known that APT downregulated the classical axis of the RAS [33] including angiotensin converting enzyme (ACE), angiotensin II (Ang II) and AT1 receptor (ACE/Ang II/AT1R axis), which is tipicaly hyperactivated in metabolic diseases such as obesity, DM and inflammation [34].