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Title: Endoplasmic Reticulum Stress Impaired Uncoupling Protein 1 Expression via the Suppression of Peroxisome Proliferator-Activated Receptor γ Binding Activity in Mice Beige Adipocytes
Authors: Yuliana, Ana
Daijo, Asumi
Jheng, Huei-Fen  kyouindb  KAKEN_id
Kwon, Jungin
Nomura, Wataru  kyouindb  KAKEN_id
Takahashi, Haruya  kyouindb  KAKEN_id  orcid (unconfirmed)
Ara, Takeshi  kyouindb  KAKEN_id  orcid (unconfirmed)
Kawada, Teruo
Goto, Tsuyoshi  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 野村, 亘
高橋, 春弥
荒, 武
河田, 照雄
後藤, 剛
Keywords: beige adipocytes
endoplasmic reticulum stress
peroxisome proliferator-activated receptor γ
uncoupling protein 1
Issue Date: 2-Jan-2019
Publisher: MDPI AG
Journal title: International Journal of Molecular Sciences
Volume: 20
Issue: 2
Thesis number: 274
Abstract: Endoplasmic reticulum (ER) homeostasis is critical in maintaining metabolic regulation. Once it is disrupted due to accumulated unfolded proteins, ER homeostasis is restored via activation of the unfolded protein response (UPR); hence, the UPR affects diverse physiological processes. However, how ER stress influences adipocyte functions is not well known. In this study, we investigated the effect of ER stress in thermogenic capacity of mice beige adipocytes. Here, we show that the expression of uncoupling protein 1 (Ucp1) involved in thermoregulation is severely suppressed under ER stress conditions (afflicted by tunicamycin) in inguinal white adipose tissue (IWAT) both in vitro and in vivo. Further investigation showed that extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were both activated after ER stress stimulation and regulated the mRNA levels of Ucp1 and peroxisome proliferator-activated receptor γ (Pparγ), which is known as a Ucp1 transcriptional activator, in vitro and ex vivo. We also found that Pparγ protein was significantly degraded, reducing its recruitment to the Ucp1 enhancer, thereby downregulating Ucp1 expression. Additionally, only JNK inhibition, but not ERK, rescued the Pparγ protein. These findings provide novel insights into the regulatory effect of ER stress on Ucp1 expression via Pparγ suppression in beige adipocytes.
Rights: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
DOI(Published Version): 10.3390/ijms20020274
PubMed ID: 30641938
Appears in Collections:Journal Articles

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