MC4R and type 2 diabetes mellitus: It has been shown in healthy, overweight, or obese mice and primates that osteoblast-derived LCN2 can cross the blood-brain barrier and bind to melanocortin receptor 4 (MC4R) on neurons in the paraventricular and ventromedial nuclei of the hypothalamus, activating the anorexigenic pathway, and suppressing appetite (Mosialou et al. 2017, 2020; Petropoulou et al. 2020); However, in T2D the role of LCN2 on appetite control is unclear and its effects on metabolism are controversial.