Ghorpade et al. proposed a mechanism where obesity triggers a Ca2+-CaMKII-ATF4 (calcium-calmodulin-dependent protein kinase II-activating transcription factor 4) pathway in the liver, leading to DDP-4 secretion, which then stimulates a CAV1-IRAK1-TAK1 (interleukin-1 receptor-associated kinase1-TGFβ activated kinase 1) pathway in ATMs, promoting ERK1/2-NFκB-mediated inflammation. The gene discussed is CAV1; the disease is obesity due to melanocortin 4 receptor deficiency.