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Aug 28, 2008

Fat Cells Show Greater Level of Stress in Obese People

  • Fat cells in obese peope appear to working improperly compared to fat cells in lean people, according to scientists at Temple University School of Medicine.

    “The fat cells we found in our obese patients were deficient in several areas,” says Guenther Boden, M.D., professor of medicine and the lead author of the study. “They showed significant stress on the endoplasmic reticulum (ER), and the tissue itself was more inflamed than in our lean patients.”

    The researchers discovered that fat cells from obese people showed an upregulation in several proteins. In particular they point to phospho c-jun NH2-terminal kinase (JNK)-1, which is known to inhibit insulin action and activate proinflammatory pathways. The investigators thus suggest that ER stress activation of JNK may be a link between obesity, insulin resistance, and inflammation.

    The findings also represent the first demonstration of unfolded protein response (UPR) activation in subcutaneous adipose tissue of obese people, according to the scientists.

    The team took fat biopsies from the upper thighs of six lean and six obese patients. They used 2-D gel and MALDI-TOF/TOF, Western blot, and RT-PCR analysis.

    Proteomic analysis revealed 19 differentially upregulated proteins in fat of obese subjects. Western blotting revealed upregulation of several other UPR stress–related proteins including JNK-1. RT-PCR analysis revealed upregulation of three other proteins.

    The study is published in the September issue of Diabetes.

    The investigators are now looking at whether free fatty acids are a potential cause for this ER stress.



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