Glucose starvation and hypoxia, but not the saturated fatty acid palmitic acid or cholesterol, activate the unfolded protein response in 3T3-F442A and 3T3-L1 adipocytes

Mihai, A.D.; Schröder, M.

Abstract

Obesity is associated with endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) in adipose tissue. In this study we identify physiological triggers of ER stress and of the UPR in adipocytes in vitro. We show that two markers of adipose tissue remodelling in obesity, glucose starvation and hypoxia, cause ER stress in 3T3-F442A and 3T3-L1 adipocytes. Both conditions induced molecular markers of the IRE1α and PERK branches of the UPR, such as splicing of XBP1 mRNA and CHOP, as well as transcription of the ER stress responsive gene BiP. Hypoxia also induced an increase in phosphorylation of the PERK substrate eIF2α. By contrast, physiological triggers of ER stress in many other cell types, such as the saturated fatty acid palmitic acid, cholesterol, or several inflammatory cytokines including TNF-α, IL-1β, and IL-6, do not cause ER stress in 3T3-F442A and 3T3-L1 adipocytes. Our data suggest that physiological changes associated with remodelling of adipose tissue in obesity, such as hypoxia and glucose starvation, are more likely physiological ER stressors of adipocytes than the lipid overload or hyperinsulinemia associated with obesity.

Citation

Mihai, A., & Schröder, M. (2015). Glucose starvation and hypoxia, but not the saturated fatty acid palmitic acid or cholesterol, activate the unfolded protein response in 3T3-F442A and 3T3-L1 adipocytes. Adipocyte, 4(3), 188-202. https://doi.org/10.4161/21623945.2014.989728

• Journal Article Type: Article
• Acceptance Date: Nov 14, 2014
• Online Publication Date: Jan 12, 2015
• Publication Date: Jan 12, 2015
• Deposit Date: Nov 17, 2014
• Publicly Available Date: Nov 20, 2014
• Journal: Adipocyte
• Print ISSN: 2162-3945
• Electronic ISSN: 2162-397X
• Publisher: Taylor and Francis Group
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 3
• Pages: 188-202
• DOI: https://doi.org/10.4161/21623945.2014.989728
• Keywords: Adipocyte, Diabetes, Glucose starvation, Hypoxia, Obesity, Unfolded protein response.
• Public URL: https://durham-repository.worktribe.com/output/1419847