Abstract
The biogenic amine serotonin is a signaling molecule in the gastrointestinal tract, platelets, and nervous tissue. In nervous system, serotonin and its metabolites are under the control of the circadian timing system, but it is not known if daily variations of serotonin exist in the liver. To explore this possibility, we tested if the rhythmic pattern of serotonin metabolism was regulated by daytime restricted feeding (DRF) which is a protocol associated to the expression of the food entrained oscillator (FEO). The DRF involved food access for 2 h each day for 3 weeks. Control groups included food ad libitum (AL) as well as acute fasting and refeeding. Serotonin-related metabolites were measured by high pressure liquid chromatography, the anabolic and catabolic enzymes were evaluated by western blot, qPCR, and immunohistochemistry to generate 24-h profiles. The results showed in the AL group, liver serotonin, tryptophan hydroxylase-1 activity, and protein abundance as well as serotonin in plasma and serum were rhythmic and coordinated. The DRF protocol disrupted this coordinated response and damped the rhythmic profile of these parameters. We demonstrated the daily synthesis and the degradation of serotonin as well as its transport in blood. This rhythm could influence the physiological role played by serotonin in peripheral organs. DRF caused an uncoordinated response in the liver and blood serotonin rhythm. This modification could be a part of the physiology of the FEO
Highlights
Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine synthesized in the neurons of the central nervous system, as well as in the enterochromaffin cells (ECs) of the gastrointestinal (GI) tract (Mawe and Hoffman 2013)
TPH exists in two isoforms, TPH-1 found in the pineal gland and peripheral organs (Sakowski et al 2006), and TPH-2 selectively expressed in brain (Walther et al 2003)
Different time points were compared using one-way analysis of variance (ANOVA), and groups were compared using a two-way ANOVA test followed in both cases by a post hoc Bonferroni test
Summary
Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine synthesized in the neurons of the central nervous system, as well as in the enterochromaffin cells (ECs) of the gastrointestinal (GI) tract (Mawe and Hoffman 2013). It regulates a variety of physiologic states and behaviors such as pain, appetite, mood, learning, sleep, vascular tone, GI motility and apoptosis, intestinal cell proliferation, and platelet aggregation (Berger et al 2009; Bertrand and Bertrand 2010). The rate limiting enzyme, tryptophan hydroxylase (or L-aromatic amino acid decarboxylase, tryptophan hydroxylase [TPH] EC 1.14.16.4.) converts L-Trp to 5-hydroxytryptophan (5-HTP), which is converted to 5-HT. 5-HT regulates several key aspects of liver function, such as hepatic blood flow, innervation, wound healing, and liver regeneration (Ruddell et al 2008; Kawasaki et al 2010)
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