Increase in Endoplasmic Reticulum Stress–Related Proteins and Genes in Adipose Tissue of Obese, Insulin-Resistant Individuals
| Autor: | Oscar Perez, Weiwei Song, Ezequiel J. Molina, Carol J. Homko, Salim Merali, Guenther Boden, Peter Cheung, Xunbao Duan |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Proteomics medicine.medical_specialty Biopsy Endocrinology Diabetes and Metabolism Subcutaneous Fat Adipose tissue 030209 endocrinology & metabolism Endoplasmic Reticulum Pathophysiology 03 medical and health sciences 0302 clinical medicine Insulin resistance Western blot Downregulation and upregulation Internal medicine Heat shock protein Internal Medicine medicine Humans Electrophoresis Gel Two-Dimensional Obesity Heat-Shock Proteins 030304 developmental biology 0303 health sciences biology medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Endoplasmic reticulum Body Weight Polysaccharides Bacterial Middle Aged medicine.disease Oxidative Stress Endocrinology Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization biology.protein Unfolded protein response Female Insulin Resistance Calreticulin |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | 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 NH2-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. |
| Databáze: | OpenAIRE |
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