Serotonin, food intake, and obesity

The role of serotonin in food intake has been studied for decades. Food intake is mainly regulated by two brain circuitries: (i) the homeostatic circuitry, which matches energy intake to energy expenditure, and (ii) the hedonic circuitry, which is involved in rewarding and motivational aspects of energy consumption. In the homeostatic circuitry, serotonergic signaling contributes to the integration of metabolic signals that convey the body's energy status and facilitates the ability to suppress food intake when homeostatic needs have been met. In the hedonic circuitry, serotonergic signaling may reduce reward-related, motivational food consumption. In contrast, peripherally acting serotonin promotes energy absorption and storage. Disturbed serotonergic signaling is associated with obesity, emphasizing the importance to understand the role of serotonergic signaling in food intake. However, unraveling the serotonin-mediated regulation of food intake is complex, as the effects of serotonergic signaling in different brain regions depend on the regional expression of serotonin receptor subtypes and downstream effects via connections to other brain regions. We therefore provide an overview of the effects of serotonergic signaling in brain regions of the homeostatic and hedonic regulatory systems on food intake. Furthermore, we discuss the disturbances in serotonergic signaling in obesity and its potential therapeutic implications.