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Cold Exposure Increases Circulating miR-122 Levels via UCP1-Dependent Mechanism in Mice

Bariuan, Jussiaea Valente Okamatsu-Ogura, Yuko Tsubota, Ayumi Matsuoka, Shinya Saito, Masayuki Kimura, Kazuhiro 北海道大学

2020.08

概要

MicroRNA(miR)-122 is highly expressed in liver and secreted into blood, which is reported to enter other tissues to modulate lipid metabolism. Brown adipose tissue (BAT) is responsible for nonshivering thermogenesis required for body temperature maintenance in cold environments. Since BAT activity is deeply related to lipid metabolism, there may be metabolic crosstalk between the liver and BAT through miR-122. In this study, we examined the effect of cold exposure on circulating miR-122 (cir-miR-122) levels in mice. Cold exposure significantly increased the expressions of Uncoupling protein 1 (Ucp1), a key molecule for thermogenesis, indicating the activation of BAT. Cold exposure significantly increased cir-miR-122 level but caused no change in miR-122 and its precursor levels in the liver. In contrast, cold exposure significantly decreased miR-122 level in the muscle, but not in BAT, suggesting that increased cir-miR-122 was due to the enhancement of its secretion from the muscle. To examine whether BAT thermogenesis was a prerequisite for increased cir-miR-122 and decreased miR-122 level in the muscle, effect of cold exposure was examined in UCP1-KO mice. While the expressions of thermogenesis-related genes in BAT, except for that of Ucp1, was increased after cold exposure, no significant changes were observed in cir-miR-122 and muscle miR-122 level in UCP1-KO mice. These results suggest that cold- induced activation of BAT thermogenesis increased cir-miR-122 through the secretion from muscle, although further study is required to find the missing link between BAT thermogenesis and miRNA secretion from the muscle.

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