PMID- 30305668
OWN - NLM
STAT- MEDLINE
DCOM- 20191023
LR  - 20191023
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Oct 10
TI  - MiR-494-3p regulates mitochondrial biogenesis and thermogenesis through PGC1-alpha 
      signalling in beige adipocytes.
PG  - 15096
LID - 10.1038/s41598-018-33438-3 [doi]
LID - 15096
AB  - 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 beta3 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 PPARgamma coactivator1-alpha (PGC1-alpha) and mitochondrial TFAM, 
      PDH, and ANT1/2 expression along with uncoupling protein-1 (Ucp1) 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 
      3T3-L1 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 Ucp1 mRNA 
      levels were robustly downregulated by miR-494-3p overexpression in 3T3-L1 beige 
      adipocytes, along with strongly decreased oxygen consumption rate. PGC1-alpha and 
      Ucp1 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 mitochondrial biogenesis and thermogenesis through PGC1-alpha.
FAU - Lemecha, Mengistu
AU  - Lemecha M
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Shiga 
      University of Medical Science, Otsu, 520-2192, Japan.
FAU - Morino, Katsutaro
AU  - Morino K
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Shiga 
      University of Medical Science, Otsu, 520-2192, Japan. 
      morino@belle.shiga-med.ac.jp.
FAU - Imamura, Takeshi
AU  - Imamura T
AD  - Division of Molecular Pharmacology, Faculty of Medicine, Tottori University, 
      Yonago, Japan.
FAU - Iwasaki, Hirotaka
AU  - Iwasaki H
AD  - Division of Pharmacology, Shiga University of Medical Science, Otsu, Japan.
FAU - Ohashi, Natsuko
AU  - Ohashi N
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Shiga 
      University of Medical Science, Otsu, 520-2192, Japan.
FAU - Ida, Shogo
AU  - Ida S
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Shiga 
      University of Medical Science, Otsu, 520-2192, Japan.
FAU - Sato, Daisuke
AU  - Sato D
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Shiga 
      University of Medical Science, Otsu, 520-2192, Japan.
FAU - Sekine, Osamu
AU  - Sekine O
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Shiga 
      University of Medical Science, Otsu, 520-2192, Japan.
FAU - Ugi, Satoshi
AU  - Ugi S
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Shiga 
      University of Medical Science, Otsu, 520-2192, Japan.
FAU - Maegawa, Hiroshi
AU  - Maegawa H
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Shiga 
      University of Medical Science, Otsu, 520-2192, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181010
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (3' Untranslated Regions)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn494 microRNA, mouse)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - 3' Untranslated Regions
MH  - 3T3-L1 Cells
MH  - Adipocytes, Beige/*metabolism
MH  - Animals
MH  - Gene Expression
MH  - Genes, Reporter
MH  - Male
MH  - Mice
MH  - MicroRNAs/*genetics
MH  - Mitochondria/*genetics/*metabolism
MH  - Models, Biological
MH  - *Organelle Biogenesis
MH  - Oxygen Consumption
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 
      1-alpha/genetics/*metabolism
MH  - RNA Interference
MH  - RNA, Messenger/genetics
MH  - *Signal Transduction
MH  - Temperature
MH  - *Thermogenesis
PMC - PMC6180067
COIS- The authors declare no competing interests.
EDAT- 2018/10/12 06:00
MHDA- 2019/10/24 06:00
PMCR- 2018/10/10
CRDT- 2018/10/12 06:00
PHST- 2018/02/16 00:00 [received]
PHST- 2018/09/05 00:00 [accepted]
PHST- 2018/10/12 06:00 [entrez]
PHST- 2018/10/12 06:00 [pubmed]
PHST- 2019/10/24 06:00 [medline]
PHST- 2018/10/10 00:00 [pmc-release]
AID - 10.1038/s41598-018-33438-3 [pii]
AID - 33438 [pii]
AID - 10.1038/s41598-018-33438-3 [doi]
PST - epublish
SO  - Sci Rep. 2018 Oct 10;8(1):15096. doi: 10.1038/s41598-018-33438-3.