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Effect of daytime-restricted feeding in the daily variations of liver metabolism and blood transport of serotonin in rat.

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.

SUBMITTER: Valdes-Fuentes M

PROVIDER: S-EPMC4463822 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Effect of daytime-restricted feeding in the daily variations of liver metabolism and blood transport of serotonin in rat.

Valdés-Fuentes Marlen M Vera-Rivera Gabriela G De Ita-Pérez Dalia D Méndez Isabel I Miranda María Isabel MI Díaz-Muñoz Mauricio M

Physiological reports 20150501 5

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 o ...[more]

PMID: 25948822

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Project description:Glutamate dehydrogenase is an important enzyme in the hepatic regulation of nitrogen and energy metabolism. It catalyzes one of the most relevant anaplerotic reactions. Although its relevance in liver homeostasis has been widely described, its daily pattern and responsiveness to restricted feeding protocols has not been studied. We explored the daily variations of liver glutamate dehydrogenase transcription, protein, activity, and histochemical and subcellular location in a protocol of daytime food synchronization in rats. Restricted feeding involved food access for 2 h each day for three weeks. Control groups included food ad libitum as well as acute fasting (21 h fasting) and refeeding (22 h fasting followed by 2 h of food access). Glutamate dehydrogenase mRNA, protein, activity, and histological location were measured every 3 h by qPCR, Western blot, spectrophotometry, and immunohistochemistry, respectively, to generate 24-h profiles. Restricted feeding promoted higher levels of mitochondrial glutamate dehydrogenase protein and activity, as well as a loss of 24-h rhythmicity, in comparison to ad libitum conditions. The rhythmicity of glutamate dehydrogenase activity detected in serum was changed. The data demonstrated that daytime restricted feeding enhanced glutamate dehydrogenase protein and activity levels in liver mitochondria, changed the rhythmicity of its mRNA and serum activity, but without effect in its expression in hepatocytes surrounding central and portal veins. These results could be related to the adaptation in nitrogen and energy metabolism that occurs in the liver during restricted feeding and the concomitant expression of the food entrainable oscillator. Impact statement For the first time, we are reporting the changes in daily rhythmicity of glutamate dehydrogenase (GDH) mRNA, protein and activity that occur in the liver during the expression of the food entrained oscillator (FEO). These results are part of the metabolic adaptations that modulate the hepatic timing system when the protocol of daytime restricted feeding is applied. As highlight, it was demonstrated higher GDH protein and activity in the mitochondrial fraction. These results contribute to a better understanding of the influence of the FEO in the energy and nitrogen handling in the liver. They could also be significant in the pathophysiology of hepatic diseases related with circadian abnormalities.

Project description:β-catenin, the principal effector of the Wnt pathway, is also one of the cadherin cell adhesion molecules; therefore, it fulfills signaling and structural roles in most of the tissues and organs. It has been reported that β-catenin in the liver regulates metabolic responses such as gluconeogenesis and histological changes in response to obesity-promoting diets. The function and cellular location of β-catenin is finely modulated by coordinated sequences of phosphorylation-dephosphorylation events. In this article, we evaluated the levels and cellular localization of liver β-catenin variants, more specifically β-catenin phosphorylated in serine 33 (this phosphorylation provides recognizing sites for β-TrCP, which results in ubiquitination and posterior proteasomal degradation of β-catenin) and β-catenin phosphorylated in serine 675 (phosphorylation that enhances signaling and transcriptional activity of β-catenin through recruitment of different transcriptional coactivators). β-catenin phosphorylated in serine 33 in the nucleus shows day-night fluctuations in their expression level in the Ad Libitum group. In addition, we used a daytime restricted feeding (DRF) protocol to show that the above effects are sensitive to food access-dependent circadian synchronization. We found through western blot and immunohistochemical analyses that DRF protocol promoted (1) higher total β-catenins levels mainly associated with the plasma membrane, (2) reduced the presence of cytoplasmic β-catenin phosphorylated in serine 33, (3) an increase in nuclear β-catenin phosphorylated in serine 675, (4) differential co-localization of total β-catenins/β-catenin phosphorylated in serine 33 and total β-catenins/β-catenin phosphorylated in serine 675 at different temporal points along day and in fasting and refeeding conditions, and (5) differential liver zonation of β-catenin variants studied along hepatic acinus. In conclusion, the present data comprehensively characterize the effect food synchronization has on the presence, subcellular distribution, and liver zonation of β-catenin variants. These results are relevant to understand the set of metabolic and structural liver adaptations that are associated with the expression of the food entrained oscillator (FEO).

Dataset Information

Effect of daytime-restricted feeding in the daily variations of liver metabolism and blood transport of serotonin in rat.

Publications

Effect of daytime-restricted feeding in the daily variations of liver metabolism and blood transport of serotonin in rat.

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