Next Article in Journal
SLC35A5 Protein—A Golgi Complex Member with Putative Nucleotide Sugar Transport Activity
Next Article in Special Issue
Endoplasmic Reticulum (ER) Stress and Unfolded Protein Response (UPR) in Mammalian Oocyte Maturation and Preimplantation Embryo Development
Previous Article in Journal
PPP3CB Inhibits Migration of G401 Cells via Regulating Epithelial-to-Mesenchymal Transition and Promotes G401 Cells Growth
Previous Article in Special Issue
Linking Endoplasmic Reticular Stress and Alternative Splicing
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2019, 20(2), 274; https://doi.org/10.3390/ijms20020274

Endoplasmic Reticulum Stress Impaired Uncoupling Protein 1 Expression via the Suppression of Peroxisome Proliferator-Activated Receptor γ Binding Activity in Mice Beige Adipocytes

1
Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan
2
Research Unit for Physiological Chemistry, the Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto 606-8501, Japan
*
Author to whom correspondence should be addressed.
Received: 29 December 2018 / Revised: 29 December 2018 / Accepted: 8 January 2019 / Published: 11 January 2019
(This article belongs to the Special Issue Endoplasmic Reticulum Stress and Unfolded Protein Response)
Full-Text   |   PDF [3408 KB, uploaded 11 January 2019]   |  

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. View Full-Text
Keywords: beige adipocytes; endoplasmic reticulum stress; peroxisome proliferator-activated receptor γ; uncoupling protein 1 beige adipocytes; endoplasmic reticulum stress; peroxisome proliferator-activated receptor γ; uncoupling protein 1
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Yuliana, A.; Daijo, A.; Jheng, H.-F.; Kwon, J.; Nomura, W.; Takahashi, H.; Ara, T.; Kawada, T.; Goto, T. Endoplasmic Reticulum Stress Impaired Uncoupling Protein 1 Expression via the Suppression of Peroxisome Proliferator-Activated Receptor γ Binding Activity in Mice Beige Adipocytes. Int. J. Mol. Sci. 2019, 20, 274.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top