Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Su Genomic Resource Center, Medical School of Soochow University, Suzhou, Jiangsu, China.
Department of Laboratory Medicine, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
Front Endocrinol (Lausanne). 2023 Mar 6;14:1157165. doi: 10.3389/fendo.2023.1157165. eCollection 2023.
Mistimed food intake in relation to the day/night cycle disrupts the synchrony of circadian rhythms in peripheral tissues and increases the risk of metabolic diseases. However, the health effects over generations have seldom been explored. Here, we established a 10-generation mouse model that was continuously fed with daytime-restricted feeding (DRF). We performed RNA-seq analysis of mouse liver samples obtained every 4 h over a 24 h period from F2, F5 and F10 generations exposed to DRF. Multigenerational DRF programs the diurnal rhythmic transcriptome through a gain or loss of diurnal rhythmicity over generations. Gene ontology (GO) analysis of the differential rhythmic transcriptome revealed that adaptation to persistent DRF is accompanied by impaired endoplasmic reticulum (ER) stress. Consistently, a substantially higher level of folding-deficient proinsulin was observed in F10 liver tissues than in F2 and F5 liver tissues following tail vein injection. Subsequently, tunicamycin induced more hepatocyte death in F10 samples than in F2 and F5 samples. These data demonstrate that mistimed food intake could produce cumulative effects over generations on ER stress sensitivity in mice.
进食时间与昼夜节律不匹配会破坏外周组织中昼夜节律的同步性，并增加代谢性疾病的风险。然而，这种代际间的健康影响很少被探索过。在这里，我们建立了一个连续 10 代接受限时喂养（DRF）的小鼠模型。我们对暴露于 DRF 的第 2、5 和 10 代小鼠的肝组织样本进行了每 4 小时采集一次的 24 小时 RNA-seq 分析。多代 DRF 通过在代际间获得或失去昼夜节律性来调控昼夜转录组的节律性。差异节律转录组的基因本体（GO）分析表明，对持续 DRF 的适应伴随着内质网（ER）应激的损伤。一致的是，与 F2 和 F5 肝组织相比，经尾静脉注射后，F10 肝组织中折叠缺陷的胰岛素原水平明显升高。随后，用衣霉素处理时，F10 样本中的肝细胞死亡比 F2 和 F5 样本更多。这些数据表明，错误的进食时间可能会在代际间对 ER 应激敏感性产生累积效应。
