This seemingly contradictory finding to the leptin theory of body weight regulation was quickly overcome by (a) the demonstration that leptin concentration was proportional to the degree of adiposity, a necessary component of the Set-Point theory (42) and (b) a slight modification of the Set-Point explanation of obesity, which could be made with the assertion that human obesity was not caused by a lack of the signal (leptin) but rather a lack of sensitivity of the brain receptors that received the signal (43). This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.