Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
Department of Physiology, College of Medicine, Korea University, Seoul, Republic of Korea.
J Neurogenet. 2023 Mar-Dec;37(1-2):25-35. doi: 10.1080/01677063.2022.2144292. Epub 2022 Nov 22.
The rhythmic pattern of biological processes controlled by light over 24 h is termed the circadian rhythm. Disturbance of circadian rhythm due to exposure to light at night (LAN) disrupts the sleep-wake cycle and can promote cardiovascular disease, diabetes, cancer, and metabolic disorders in humans. We studied how dim LAN affects the circadian rhythm and metabolism using male . Wild-type flies exposed to the dim light of 10 lux at night displayed altered 24 h sleep-wake behavior and expression patterns of circadian rhythm genes. In addition, the flies became more vulnerable to metabolic stress, such as starvation. Whole-body metabolite analysis revealed decreased amounts of branched-chain amino acids (BCAAs), such as isoleucine and valine. The dim light exposure also increased the expression of branched-chain amino acid aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKDC) enzyme complexes that regulate the metabolism of BCAAs. Flies with the heterozygous mutation were not vulnerable to starvation stress, even when exposed to dim LAN, and hemolymph BCAA levels did not decrease in these flies. Furthermore, the vulnerability to starvation stress was also suppressed when the expression level was reduced in the whole body, neurons, or fat body during adulthood using conditional GAL4 and RNA interference. Finally, the metabolic vulnerability was reversed when BCAAs were fed to wild-type flies exposed to LAN. Thus, short-term dim light exposure at night affects the expression of circadian genes and BCAA metabolism in , implying a novel function of BCAAs in suppressing metabolic stress caused by disrupted circadian rhythm.
生物过程受光控制的 24 小时节律模式被称为昼夜节律。由于夜间光照(LAN)导致昼夜节律紊乱,会破坏睡眠-觉醒周期,并可能促进人类心血管疾病、糖尿病、癌症和代谢紊乱。我们研究了弱 LAN 如何通过影响生物钟和代谢来影响昼夜节律和代谢,使用雄性果蝇。夜间暴露在 10 勒克斯的弱光下的野生型果蝇表现出改变的 24 小时睡眠-觉醒行为和昼夜节律基因表达模式。此外,果蝇对代谢应激(如饥饿)变得更加脆弱。全身代谢物分析显示支链氨基酸(BCAA),如异亮氨酸和缬氨酸的含量减少。弱光暴露还增加了调节 BCAA 代谢的支链氨基酸氨基转移酶(BCAT)和支链 α-酮酸脱氢酶(BCKDC)酶复合物的表达。杂合突变的果蝇即使暴露在弱 LAN 下也不易受到饥饿应激,并且这些果蝇的血液 BCAA 水平没有降低。此外,当成年期在全身、神经元或脂肪体中使用条件性 GAL4 和 RNAi 降低 表达水平时,饥饿应激的脆弱性也受到抑制。最后,当向暴露于 LAN 的野生型果蝇喂食 BCAA 时,代谢脆弱性得到逆转。因此,夜间短期弱光暴露会影响 的昼夜节律基因和 BCAA 代谢表达,暗示 BCAA 在抑制由昼夜节律紊乱引起的代谢应激方面具有新的功能。