4.7 Article

Nighttime light exposure enhances Rev-erbα-targeting microRNAs and contributes to hepatic steatosis

Journal

METABOLISM-CLINICAL AND EXPERIMENTAL
Volume 85, Issue -, Pages 250-258

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2018.05.002

Keywords

Clock genes; De novo lipogenesis; Exposure to artificial light at night; Hepatic steatosis; microRNAs

Funding

  1. Sao Paulo Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [FAPESP 2013/26740-0, 2014/01717-9, 2015/12611-0]
  2. National Council for Scientific and Technological Development (Conselho Nacional para o Desenvolvimento Cientifico e Tecnologico) [CNPq - 449794/2014-8]
  3. NIH [R01DK45586]

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Objective: 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. Results: We found that C3H/HePas mice exposed to ALAN developed obesity, and hepatic steatosis, which was paralleled by decreased expression of Rev-erb alpha and up-regulation of its lipogenic targets ACL and FAS in liver. Furthermore, the expression of Rev-erb alpha-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-erb alpha expression at the mRNA and protein levels. Importantly, overexpression of Rev-erb alpha-targeting miRNAs increased mRNA levels of Acly and Fasn. Conclusion: 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. (C) 2018 Elsevier Inc. All rights reserved.

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