Metabolic and Steatohepatitis
Molecular and biochemical modifications of liver glutamine synthetase elicited by daytime restricted feeding
Version of Record online: 16 DEC 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 34, Issue 9, pages 1391–1401, October 2014
How to Cite
Liver Int. 2014: 34: 1391–1401
- Issue online: 18 SEP 2014
- Version of Record online: 16 DEC 2013
- Accepted manuscript online: 25 NOV 2013 11:25AM EST
- Manuscript Accepted: 16 NOV 2013
- Manuscript Received: 21 JUL 2013
- PAPIIT, UNAM. Grant Numbers: IA200713, IB200311
- allosteric regulation;
- daytime restricted feeding;
- food entrained oscillator;
- nitrogen metabolism
Background & Aims
The circadian clock system in the liver plays important roles in regulating metabolism and energy homeostasis. Restricted feeding schedules (RFS) become an entraining stimulus that promotes adaptations that form part of an alternative circadian clock known as the food entrained oscillator (FEO). The aim of this study was to evaluate the daily variations of glutamine synthetase (GS) in liver under a daytime RFS.
Hepatic GS properties were analysed at 3-h intervals over a 24-h period in adult male Wistar rats maintained in a 12:12 h light–dark cycle. RFS group: food access for 2-h in light phase, during 3 weeks. AL group: feeding ad libitum. Fa group: acute fast (21 h). Fa–Re group: acute fast followed by refed 2 h. mRNA expression was measured by RT-qPCR, protein presence by Western-blot and immunohistochemistry, enzyme activity by a spectrophotometric assay, and glutamine by high pressure liquid chromatography.
Results and Conclusions
Restricted feeding schedule induced circadian rhythmicity in mRNA levels of GS and the loss of the rhythmic pattern in mitochondrial GS activity. GS activity in liver homogenates displayed a robust rhythmic pattern in AL that was not modified by RFS. The presence of GS and its zonal distribution did not show rhythmic pattern in both groups. However, acute Fa and Fa–Re diminished GS protein and activity in liver homogenates. Hepatic glutamine concentrations showed a 24-h rhythmic pattern in both groups, in an antiphasic pattern. In conclusion, daytime RFS influences the liver GS system at different levels, that could be part of rheostatic adaptations associated to the FEO, and highlight the plasticity of this system.