When leptin concentrations are raised above an individual “threshold” (which is higher in individuals with obesity), the relevant neuronal tracts are less sensitive (LeDuc and Leibel, 2019; Zhao et al., 2019) and further leptin administration evokes little if any response in humans (Rosenbaum et al., 2018b). This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.