Oxidative stress is particularly harmful to the neonatal brain because of its high oxygen consumption, high contents of unsaturated fatty acids and water, low myelination, low concentrations of antioxidants, and low availability of redox-active iron 8
Targeted agonism of the MC4R with setmelanotide showed ~10% body weight loss in patients with POMC deficiency and LEPR deficiency (14), and there are case reports showing weight loss after GLP-1 therapy in individuals with pathogenic variants of MC4R (1517)
Of note, the reduction in HHF with GLP-1 RAs [4], although significant, is less than with the SGLT2is [3] and the SGLT1/2i sotagliflozin [5, 6]
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Two highly conserved glutamic acid residues in the predicted beta propeller domain of dipeptidyl peptidase IV are required for its enzyme activity