Patricia C Borck1, Thiago M Batista2, Jean F Vettorazzi2, Gabriela M Soares2, Camila Lubaczeuski2, Dongyin Guan3, Antonio C Boschero2, Elaine Vieira4, Mitchell A Lazar3, Everardo M Carneiro2. 1. 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. Electronic address: pati.0816@gmail.com. 2. 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. 3. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA. 4. Postgraduate Program in Physical Education, Universidade Católica de Brasília - UCB, DF, Brazil.
Abstract
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-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. 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.
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-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. 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.
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