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Updated: Jun 10, 2025
Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
Comparison of the Effects of Inappropriate Meal Timing-Induced and Genetic Models of Circadian Clock Disruption on
Yuchen Chen1, Takashi Hosono1, Masanori Ono2
1Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Background:
Accumulating evidence reveals that inappropriate meal timing contributes to the development of lifestyle-related diseases. An underlying mechanism is thought to be the disruption of the intracellular circadian clock in various tissues based on observations in both systemic and tissue-specific clock gene-deficient mice. However, whether the effects of conditional clock gene knockout are comparable to those of inappropriate meal timing remains unclear.
Objectives:
This study aimed to compare the effects of a recently developed 28-h feeding cycle model with those of a core clock gene Bmal1 uterine conditional knockout (Bmal1 cKO) model on uterine mRNA expression profiles.
Methods:
The models were generated by subjecting C57BL/6J mice to an 8-h/20-h feeding/fasting cycle for 2 wk and crossing Bmal1-floxed mice with PR-Cre mice. Microarray analyses were conducted using uterine samples obtained at the beginning of the dark and light periods.
Results:
The analyses identified 516 and 346, significantly 4-fold and 2-fold, up- or downregulated genes in the 28-h feeding cycle and Bmal1 cKO groups, respectively, compared with each control group. Among these genes, only 7 (1.4%) and 63 (18.2%) were significantly up- or downregulated in the other model. Moreover, most (n = 44, 62.9%) of these genes were oppositely regulated. These findings were confirmed by gene set enrichment analyses.
Conclusions:
This study reveals that a 28-h feeding cycle and Bmal1 cKO differently affect gene expression profiles and highlights the need for considering this difference to assess the pathophysiology of diseases associated with inappropriate meal timing.
Insights
Altered meal timing and Bmal1 gene knockout differently impact uterine gene expression. Understanding these distinct effects is crucial for studying diseases linked to circadian rhythm disruption.
Area of Science:
- Chronobiology
- Molecular Biology
- Genetics
Background:
- Inappropriate meal timing is linked to lifestyle diseases, potentially via circadian clock disruption.
- Previous studies used clock gene knockout models, but direct comparison with meal timing disruption is lacking.
Purpose of the Study:
- To compare gene expression changes in the uterus caused by a 28-hour feeding cycle versus Bmal1 uterine conditional knockout (Bmal1 cKO).
Main Methods:
- Mice were subjected to a 28-hour feeding cycle or Bmal1 cKO.
- Uterine mRNA expression was analyzed using microarrays at specific time points.
Main Results:
- The 28-hour feeding cycle and Bmal1 cKO models induced distinct gene expression profiles in the uterus.
- A small overlap of differentially expressed genes was observed between the two models, with many showing opposite regulation.
Conclusions:
- A 28-hour feeding cycle and Bmal1 cKO have divergent effects on uterine gene expression.
- These differences must be considered when investigating diseases related to disrupted circadian rhythms and meal timing.
