期刊
SCIENTIFIC REPORTS
卷 8, 期 -, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41598-018-33438-3
关键词
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资金
- Japanese government
- Japan Society for the Promotion of Science [25461342, 15K08229, 17K17814]
- Department of Medicine, SUMS
- Boehringer-Ingelheim
- MSD
- Novo-Nordisk
- Pfizer
- Sanofi
- Takeda
- Astellas
- Grants-in-Aid for Scientific Research [25461342, 17K17814, 15K08229] Funding Source: KAKEN
Mitochondria are critical in heat generation in brown and beige adipocytes. Mitochondrial number and function are regulated in response to external stimuli, such as cold exposure and beta 3 adrenergic receptor agonist. However, the molecular mechanisms regulating mitochondrial biogenesis during browning, especially by microRNAs, remain unknown. We investigated the role of miR-494-3p in mitochondrial biogenesis during adipogenesis and browning. Intermittent mild cold exposure of mice induced PPAR gamma coactivatorl-alpha (PGC1-alpha) and mitochondrial TFAM, PDH, and ANT1/2 expression along with uncoupling protein-1(Ucpl) in inguinal white adipose tissue (iWAT). miR-494-3p levels were significantly downregulated in iWAT upon cold exposure (p < 0.05). miR-494-3p overexpression substantially reduced PGC1-alpha. expression and its downstream targets TFAM, PDH and MTCO1 in 3T3Ll white and beige adipocytes (p < 0.05). miR-494-3p inhibition in 3T3-L1 white adipocytes resulted in increased PDH (p < 0.05). PGC1-alpha.,TFAM and Ucpl mRNA levels were robustly downregulated by miR494-3p overexpression in 3T3-L1 beige adipocytes, along with strongly decreased oxygen consumption rate. PGC1-alpha. and Ucpl proteins were downregulated by miR-494-3p in primary beige cells (p < 0.05). Luciferase assays confirmed PGC1-alpha. as a direct gene target of miR-494-3p. Our findings demonstrate that decreased miR-494-3p expression during browning regulates mitochondria! biogenesis and thermogenesis through PGC1-alpha.
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