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Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals.
Boden, Guenther; Duan, Xunbao; Homko, Carol; Molina, Ezequiel J; Song, WeiWei; Perez, Oscar; Cheung, Peter; Merali, Salim.
Affiliation
  • Boden G; Division of Endocrinology, Diabetes, and Metabolism and the Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. bodengh@tuhs.temple.edu
Diabetes ; 57(9): 2438-44, 2008 Sep.
Article in En | MEDLINE | ID: mdl-18567819
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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Insulin Resistance / Oxidative Stress / Proteomics / Endoplasmic Reticulum / Subcutaneous Fat / Obesity Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Diabetes Year: 2008 Document type: Article Affiliation country: United States Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Insulin Resistance / Oxidative Stress / Proteomics / Endoplasmic Reticulum / Subcutaneous Fat / Obesity Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Diabetes Year: 2008 Document type: Article Affiliation country: United States Country of publication: United States