Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas/UNICAMP, Campinas, SP, Brazil; Department of Structural and Functional Biology, Institute of Biology, University of Campinas/UNICAMP, Campinas, SP, Brazil.
Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas/UNICAMP, Campinas, SP, Brazil; Department of Structural and Functional Biology, Institute of Biology, University of Campinas/UNICAMP, Campinas, SP, Brazil.
Metabolism. 2018 Aug;85:250-258. doi: 10.1016/j.metabol.2018.05.002. Epub 2018 May 8.
The exposure to artificial light at night (ALAN) disrupts the biological rhythms and has been associated with the development of metabolic syndrome. MicroRNAs (miRNAs) display a critical role in fine-tuning the circadian system and energy metabolism. In this study, we aimed to assess whether altered miRNAs expression in the liver underlies metabolic disorders caused by disrupted biological rhythms.
We found that C3H/HePas mice exposed to ALAN developed obesity, and hepatic steatosis, which was paralleled by decreased expression of Rev-erbα and up-regulation of its lipogenic targets ACL and FAS in liver. Furthermore, the expression of Rev-erbα-targeting miRNAs, miR-140-5p, 185-5p, 326-5p and 328-5p were increased in this group. Consistently, overexpression of these miRNAs in primary hepatocytes reduced Rev-erbα expression at the mRNA and protein levels. Importantly, overexpression of Rev-erbα-targeting miRNAs increased mRNA levels of Acly and Fasn.
Thus, altered miRNAs profile is an important mechanism underlying the disruption of the peripheral clock caused by exposure to ALAN, which could lead to hepatic steatosis.
夜间人工光照(ALAN)会扰乱生物节律,并与代谢综合征的发展有关。microRNAs(miRNAs)在精细调节生物钟和能量代谢方面发挥着关键作用。在这项研究中,我们旨在评估肝脏中 miRNA 表达的改变是否是由生物节律紊乱引起的代谢紊乱的基础。
我们发现,暴露于 ALAN 的 C3H/HePas 小鼠发生肥胖和肝脂肪变性,这与肝脏中 Rev-erbα 的表达降低和其脂肪生成靶标 ACL 和 FAS 的上调相平行。此外,在该组中,Rev-erbα 靶向 miRNA,miR-140-5p、185-5p、326-5p 和 328-5p 的表达增加。一致地,这些 miRNA 在原代肝细胞中的过表达降低了 Rev-erbα 在 mRNA 和蛋白水平的表达。重要的是,Rev-erbα 靶向 miRNA 的过表达增加了 Acly 和 Fasn 的 mRNA 水平。
因此,miRNA 谱的改变是 ALAN 暴露导致外周时钟破坏的重要机制,可能导致肝脂肪变性。