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Hypoxia in 3T3-L1 adipocytes suppresses adiponectin expression via the PERK and IRE1 unfolded protein response.

Abstract
Adiponectin, an adipocytokine produced by adipocytes, functions as an anti-inflammatory and anti-apoptotic substance, while also enhancing insulin sensitivity. Patients or model animals with obesity or diabetes typically present attenuated expression of adiponectin. Moreover, obesity and diabetes are often accompanied with hypoxia in adipose tissue, which may result in endoplasmic reticulum (ER) stress as well as low expression of adiponectin. The purpose of this study was to investigate the specific role of the unfolded protein response (UPR) involved in the low expression of adiponectin induced by hypoxia. Subjecting 3T3-L1 adipocytes to hypoxia significantly reduced adiponectin expression and activated the PERK and IRE1 signaling pathways in a time-dependent manner. The ATF6 signaling pathway showed no obvious changes with hypoxia treatment under a similar time course. Moreover, the down-regulated expression of adiponectin induced by hypoxia was relieved once the PERK and IRE1 signaling pathways were suppressed by the inhibitors GSK2656157 and 4μ8C, respectively. Overall, these data demonstrate that hypoxia can suppress adiponectin expression and activate the PERK and IRE1 signaling pathways in differentiated adipocytes, and this two pathways are involved in the suppression of adiponectin expression induced by hypoxia.
AuthorsQian Guo, Sanli Jin, Hailong Hu, Ying Zhou, Yuheng Yan, He Zong, Yu Wang, Hongjuan He, Yuri Oh, Chuanpeng Liu, Ning Gu
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 493 Issue 1 Pg. 346-351 (11 04 2017) ISSN: 1090-2104 [Electronic] United States
PMID28888981 (Publication Type: Journal Article)
CopyrightCopyright © 2017 Elsevier Inc. All rights reserved.
Chemical References
  • Adiponectin
  • Membrane Proteins
  • Ern2 protein, mouse
  • PERK kinase
  • Protein Serine-Threonine Kinases
  • eIF-2 Kinase
  • Oxygen
Topics
  • 3T3-L1 Cells
  • Adiponectin (metabolism)
  • Animals
  • Cell Hypoxia (physiology)
  • Down-Regulation (physiology)
  • Membrane Proteins (metabolism)
  • Mice
  • Oxygen (metabolism)
  • Protein Serine-Threonine Kinases (metabolism)
  • Signal Transduction (physiology)
  • Unfolded Protein Response (physiology)
  • eIF-2 Kinase (metabolism)

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