Chen Yuchen, Hosono Takashi, Ono Masanori, Daikoku Takiko, Toyoda Natsumi, Nomura Satoshi, Kagami Kyosuke, Orisaka Shunsuke, Horike Shin-Ichi, Shi Yifan, Xu Pingping, Morishige Jun-Ichi, Fujiwara Tomoko, Fujiwara Hiroshi, Ando Hitoshi
Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan.
J Nutr. 2024 Dec;154(12):3718-3725. doi: 10.1016/j.tjnut.2024.10.011. Epub 2024 Oct 10.
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.
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.
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.
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.
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.
越来越多的证据表明，不适当的进餐时间会导致与生活方式相关疾病的发生。基于对全身和组织特异性生物钟基因敲除小鼠的观察，一种潜在机制被认为是各种组织中细胞内生物钟的紊乱。然而，条件性生物钟基因敲除的影响是否与不适当的进餐时间的影响相当仍不清楚。
本研究旨在比较最近开发的28小时喂养周期模型与核心生物钟基因Bmal1子宫条件性敲除（Bmal1 cKO）模型对子宫mRNA表达谱的影响。
通过使C57BL/6J小鼠接受8小时/20小时的喂养/禁食周期，持续2周，并将Bmal1基因敲除小鼠与PR-Cre小鼠杂交来构建模型。使用在黑暗期和光照期开始时获得的子宫样本进行微阵列分析。
分析确定，与每个对照组相比，在28小时喂养周期组和Bmal1 cKO组中分别有516个和346个基因显著上调或下调4倍和2倍。在这些基因中，在另一个模型中只有7个（1.4%）和63个（18.2%）基因显著上调或下调。此外，这些基因中的大多数（n = 44，62.9%）受到相反的调节。这些发现通过基因集富集分析得到了证实。
本研究表明，28小时喂养周期和Bmal1 cKO对基因表达谱的影响不同，并强调在评估与不适当进餐时间相关疾病的病理生理学时需要考虑这种差异。
