Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals
Open accessAbstract
OBJECTIVE: To examine fat biopsy samples from lean insulin-sensitive and obese insulin-resistant nondiabetic individuals for evidence of endoplasmic reticulum (ER) stress. RESEARCH DESIGN AND METHODS: Subcutaneous fat biopsies were obtained from the upper thighs of six lean and six obese nondiabetic subjects. Fat homogenates were used for proteomic (two-dimensional gel and MALDI-TOF/TOF), Western blot, and RT-PCR analysis. RESULTS: Proteomic analysis revealed 19 differentially upregulated proteins in fat of obese subjects. Three of these proteins were the ER stress-related unfolded protein response (UPR) proteins calreticulin, protein disulfide-isomerase A3, and glutathione-S-transferase P. Western blotting revealed upregulation of several other UPR stress-related proteins, including calnexin, a membrane-bound chaperone, and phospho c-jun NH(2)-terminal kinase (JNK)-1, a downstream effector protein of ER stress. RT-PCR analysis revealed upregulation of the spliced form of X-box binding protein-1s, a potent transcription factor and part of the proximal ER stress sensor inositol-requiring enzyme-1 pathway. CONCLUSIONS: These findings represent the first demonstration of UPR activation in subcutaneous adipose tissue of obese human subjects. As JNK can inhibit insulin action and activate proinflammatory pathways, ER stress activation of JNK may be a link between obesity, insulin resistance, and inflammation.
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Endoplasmic-reticulum stress pathways are activated in rodent models of obesity and in human obesity.
“Their activation has been shown in rodent models of obesity129 and in human obesity.130”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [130]
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- Authors
- Boden, G., Duan, X., Homko, C., Molina, E. J., Song, W., Perez, O., Cheung, P., & Merali, S.
- Affiliations
- Temple University (US)
- Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania
- Corresponding author
- Boden, Guenther
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-09-01
- Volume
- 57
- Issue
- 9
- Pages
- 2438-2444
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2518495
- OpenAlex
- W2147127785
- Cited by
- 468
- References
- 34
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 25 · 2023: 18 · 2022: 15 · 2021: 17 · 2020: 31 · 2019: 18 · 2018: 32 · 2017: 38 · 2016: 27 · 2015: 26 · 2014: 31 · 2013: 46 · 2012: 34
- FWCI
- 12.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- Mary E. Groff Surgical and Medical Research and Education Charitable Trust
- National Institutes of Health (HL-0733267)
- U.S. Public Health Service (R01-A1064017)
- National Heart, Lung, and Blood Institute (HL-0733267)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK58895, R01DK066003, R01DK058895)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- endoplasmic reticulum stress, unfolded protein response, subcutaneous adipose tissue, obesity, insulin resistance, calreticulin, protein disulfide isomerase A3, glutathione S-transferase pi, calnexin, JNK1, inflammation, adipose tissue proteome
- MeSH terms
- Adult, Biopsy, Body Weight, Endoplasmic Reticulum, Female, Heat-Shock Proteins, Humans, Insulin Resistance, Male, Middle Aged, Obesity, Polysaccharides, Bacterial, Electrophoresis, Gel, Two-Dimensional, Oxidative Stress, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Proteomics, Subcutaneous Fat
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