Henan Eye Institute, Henan Eye Hospital and Henan Key Laboratory of Ophthalmology and Visual Science, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou City, China.
Invest Ophthalmol Vis Sci. 2022 May 2;63(5):23. doi: 10.1167/iovs.63.5.23.
A high-fat diet (HFD) increases the risk of developing many systemic diseases; however, the effects of high fat intake on lacrimal gland functions and the molecular mechanisms underlying these effects are unknown. We explored the effects of an HFD on the circadian rhythms of the extraorbital lacrimal glands (ELGs).
Male C57BL/6J mice maintained on a 12/12-hour light/dark cycle were fed an ad libitum HFD or normal chow (NC) for 2 weeks. The ELGs were collected from euthanized animals every 3 hours throughout the circadian cycle (24 hours). Using high-throughput RNA-sequencing (RNA-Seq), we studied the circadian transcriptomic profile of the ELGs. Circadian oscillations in cell size, secretion response, lipid deposition, and immune cell trafficking of the ELGs were also analyzed.
An HFD modulated the circadian transcriptomic profile of the ELGs, including the composition, phase, and amplitude of cyclical transcript oscillations, and affected the associated signaling pathways at spatiotemporal levels. HFD feeding significantly altered the normal rhythmic oscillations of ELG cell size, immune cell trafficking, secretion response, and lipid deposition. After dietary reversal in HFD-fed animals, the activity, core temperature, and lipid accumulation in lacrimal glands recovered partially to the level of NC-fed animals. However, the average cell size of the ELGs, the recruitment of immune cells, and the rhythm of lacrimal secretion did not return to the levels of the NC-fed group.
HFD perturbation interferes with the cyclical transcriptomic profile, cell size, immune cell trafficking, and secretion function of the ELGs with a strikingly high sensitivity.
高脂肪饮食（HFD）会增加许多系统性疾病的发病风险；然而，高脂肪摄入对泪腺功能的影响以及这些影响的潜在分子机制尚不清楚。我们研究了 HFD 对眼外泪腺（ELG）昼夜节律的影响。
雄性 C57BL/6J 小鼠在 12/12 小时光照/黑暗周期下自由进食 HFD 或正常饲料（NC）2 周。从安乐死动物中每隔 3 小时收集一次整个昼夜周期（24 小时）的 ELG。使用高通量 RNA 测序（RNA-Seq），我们研究了 ELG 的昼夜转录组谱。还分析了 ELG 细胞大小、分泌反应、脂质沉积和免疫细胞迁移的昼夜节律波动。
HFD 调节了 ELG 的昼夜转录组谱，包括循环转录波动的组成、相位和幅度，以及在时空水平上影响相关信号通路。HFD 喂养显著改变了 ELG 细胞大小、免疫细胞迁移、分泌反应和脂质沉积的正常节律波动。在 HFD 喂养动物的饮食逆转后，泪腺的活性、核心体温和脂质积累部分恢复到 NC 喂养动物的水平。然而，ELG 的平均细胞大小、免疫细胞募集和泪液分泌的节律并未恢复到 NC 喂养组的水平。
HFD 干扰了 ELG 的周期性转录组谱、细胞大小、免疫细胞迁移和分泌功能，其敏感性极高。
