In addition to the classical mTOR, NF-κB, JNK, and PI3K/Akt pathway, a COX-2-dependent mechanism has also been found to modulate macrophage polarization in the development of post-incisional pain, obesity-associated insulin resistance and Hirschsprung disease-associated Enterocolitis (Meng et al., 2024; Godai et al., 2014; Chan et al., 2018). Here, AKT1 is linked to obesity due to melanocortin 4 receptor deficiency.