Serotonin, food intake, and obesity

Abstract

Summary 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.

Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

“…For instance, we find that the serotonin transporter is consistently implicated in OCD and bipolar disorder, consistent with the fact that selective serotonin reuptake inhibitors (SSRI) are frequently used to treat such disorders-although we do not find a significant spatial relationship between the serotonin transporter and depression. Additionally, we find that serotonin receptors are associated with obesity, consistent with the notion that serotonin systems regulate homeostatic and hedonic circuitry and are therefore implicated in food intake [141]. On the other hand, we find associations that have some preliminary support in the literature, but to our knowledge have not been conclusively established and adopted into clinical practice, including histamine H 3 in Parkinson's disease [102,116], MOR in ADHD [23,105], and D 1 and NET in temporal lobe epilepsy [20,44,129].…”

Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

“…For instance, we find that the serotonin transporter is consistently implicated in OCD and bipolar disorder, consistent with the fact that selective serotonin reuptake inhibitors (SSRI) are frequently used to treat such disorders. Additionally, we find that serotonin receptors are associated with obesity, consistent with the notion that serotonin systems regulate homeostatic and hedonic circuitry and are therefore implicated in food intake [133]. On the other hand, we find associations that have some preliminary support in the literature, but to our knowledge have not been conclusively established and adopted into clinical practice, including histamine H 3 in Parkinson's disease [95,108], MOR in ADHD [23,98], and D 1 and NET in temporal lobe epilepsy [20,42,121].…”

The response to prolonged fasting in hypothalamic serotonin transporter availability is blunted in obesity

“…Changes in serotonergic and/or dopaminergic signaling are hypothesized to contribute to obesity [17,18]. Reduced postprandial serotonergic signaling results in insufficient inhibition of additional food intake (i.e., beyond homeostatic needs) [19,20]. In turn, postprandial striatal dopamine release is blunted in diet-induced obese mice, suggesting a reduction in the rewarding aspects of food intake; this may promote a compensational increase in food intake [21].…”