title: 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.
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.
authors.affiliation: School of Biological and Biomedical Sciences; Durham University ; Durham, United Kingdom ; Biophysical Sciences Institute; Durham University ; Durham, United Kingdom ; North East England Stem Cell Institute (NESCI); Life Bioscience Center; International Center for Life; Central Parkway ; Newcastle Upon Tyne, United Kingdom.
authors.forename: Adina D
authors.initials: AD
authors.lastname: Mihai
authors.affiliation: School of Biological and Biomedical Sciences; Durham University ; Durham, United Kingdom ; Biophysical Sciences Institute; Durham University ; Durham, United Kingdom ; North East England Stem Cell Institute (NESCI); Life Bioscience Center; International Center for Life; Central Parkway ; Newcastle Upon Tyne, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Schröder
keywords: adipocyte; diabetes; glucose starvation; hypoxia; obesity; unfolded protein response