Serotonin and the regulation of mammalian energy balance

Abstract

Maintenance of energy balance requires regulation of the amount and timing of food intake. Decades of experiments utilizing pharmacological and later genetic manipulations have demonstrated the importance of serotonin signaling in this regulation. Much progress has been made in recent years in understanding how central nervous system (CNS) serotonin systems acting through a diverse array of serotonin receptors impact feeding behavior and metabolism. Particular attention has been paid to mechanisms through which serotonin impacts energy balance pathways within the hypothalamus. How upstream factors relevant to energy balance regulate the release of hypothalamic serotonin is less clear, but work addressing this issue is underway. Generally, investigation into the central serotonergic regulation of energy balance has had a predominantly “hypothalamocentric” focus, yet non-hypothalamic structures that have been implicated in energy balance regulation also receive serotonergic innervation and express multiple subtypes of serotonin receptors. Moreover, there is a growing appreciation of the diverse mechanisms through which peripheral serotonin impacts energy balance regulation. Clearly, the serotonergic regulation of energy balance is a field characterized by both rapid advances and by an extensive and diverse set of central and peripheral mechanisms yet to be delineated.

Kynurenine pathway metabolism and the microbiota-gut-brain axis

“…In addition, 5-HT mediates feelings of nausea and can induce vomiting by stimulating 5-HT3 receptors on vagal afferent pathways which signal to the nucleus tractus solitarii (Klatt et al, 1999;Talley et al, 1990). In addition, peripheral 5-HT release in the GI tract can modulate food intake by stimulating vagal afferent pathways (Donovan and Tecott, 2013) and inhibition of peripherial 5-HT synthesis has been shown to reduce obesity and metabolic dysfunction through actions on brown adipose tissue thermogenesis (Crane et al, 2015). In the CNS, 5-HT is involved in a range of mood, behavioural and cognitive functions, and is the purported target of many psychiatric medications (Berger et al, 2009;Cryan and Leonard, 2000).…”

Serotonin controlling feeding and satiety

“…These studies should integrate models of diet induced obesity at different stages of obesity as possible interactions between leptin and 5-HT may change during development. Even if it remains controversial if 5-HT interacts with leptin at the neuronal level [287], evidence has been provided that 5-HT and leptin act in concert, possibly via a functional synergism at the interface between episodic and tonic satiety.…”

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

“…Ak and colleagues also reported that the plasma POMC level was elevated in first attack psychotic male patients treated with olanzapine, but no changes in plasma CART level were observed [100]. It should be noted that olanzapine suppresses POMC expression by blocking 5-HT 2C R, and indirectly blocking 5-HT 1B receptors (5-HT 1B R), while that suppression is abolished by GABA (gamma-aminobutyric acid) neurons [161] (summarised in Figure 1). However, a recent genetic study reported that neither the POMC single nucleotide polymorphisms (SNPs) (rs6713532, rs1047521, rs3754860) nor the CART SNP (rs10515115, rs3763153, rs3857384, rs11575893, rs16871471) gene variants was associated with weight gain in chronic schizophrenia patients treated with SGAs [162].…”