Serotonin, obesity and diabetes mellitus: Is there any link?

Serotonin (5-HT) is an important, ubiquitous neurotransmitter found in several parts of the central and peripheral nervous systems. It is also abundant in the APUD cells of the gastrointestinal tract. Serotonin acts via 14 different receptors belonging to 7 subfamilies (5-HT_1-7). Several studies have shown that serotonin plays a role in the regulation of body weight and feeding. Moreover, it is well known that long-term use of selective serotonin reuptake inhibitors (SSRIs), significantly increases body weight gain. In contrast, stimulation of 5-HT_2C receptor agonists, such as fenfluramine, leads to significant weight loss. In view of this, the serotonergic system has been a focus for medications that could reduce obesity and its complications, such as diabetes mellitus. The probable mechanism by which serotonin reduces weight is three fold. Serotonin reduces body weight by inducing hypophagia via the hypothalamic melanocortin system. This action is probably mediated through a number of neuropeptides such as leptin, ghrelin and neuropeptide-Y. The other pathway is the ability of serotonin to stimulate insulin sensitivity and release, which in turn will help in the metabolism of glucose. In conclusion, serotonin and its agonists can play a role in the therapeutic management of obesity and its complications.