Regulation of Appetite: Role of Serotonin and Hypothalamus

Serotonin (5-HT), a mono-aminergic neurotransmitter is biochemically derived from tryptophan and is mainly found in gastrointestinal tract, platelets and central nervous system of animals. Serotonin (5-HT) in coordination with hypothalamus plays an important role in the CNS control of appetite, eating behavior, and energy balance and body weight. It has a special role in control of carbohydrate intake. It has been observed that reduction in serotonin level causes hyperphagia. As the result, carbohydrate intake increases and hence results in obesity. Inversely-increased level of serotonin level leads to hypophagia, as a result carbohydrate intake decreases. That is why serotonergic agonists are clinically useful in treatment of obesity. Obesity (body mass index [BMI] > 30) is a risk factor for major causes of death, including cardiovascular disease, numerous cancers, diabetes, and metabolic syndrome and is linked with markedly diminished life expectancy. The energy regulation of 5-HT is mediated in part, by 5-HT receptors located in various medial hypothalamic nuclei. Along with serotonin, other hormones like insulin; leptin and corticosteron are also involved in the energy control and regulation. Though large numbers of serotonergic drug like selective serotonin reuptake inhibitors (SSRI), such as sibutramine, or serotonin 5HT2c agonists are available to treat this deadly disease, these drugs are associated with large number of side effects. Thus, the increasing global prevalence of obesity has renewed interest in the serotonin-hypothalamic regulation of energy balance to find the drugs having maximum pharmacological and minimum toxicological effects. In this review article, attempts have been made to provide the detailed role of serotonin in the appetite regulation so that new targets and new sites can be created for the therapy of obesity.