Similarly, in randomized clinical trials, modulation of this regulatory circuitry triggered by oral ingestion of acetylcholinesterase inhibitors has been shown to play a role in alleviating obesity-induced comorbidities in humans (155, 156), suggesting that modulating this circuitry may be an effective method of controlling obesity and obesity-related diseases. Here, ACHE is linked to obesity due to melanocortin 4 receptor deficiency.