title: Increased adipose protein carbonylation in human obesity.
abstract: Insulin resistance is associated with obesity but mechanisms controlling this relationship in humans are not fully understood. Studies in animal models suggest a linkage between adipose reactive oxygen species (ROS) and insulin resistance. ROS oxidize cellular lipids to produce a variety of lipid hydroperoxides that in turn generate reactive lipid aldehydes that covalently modify cellular proteins in a process termed carbonylation. Mammalian cells defend against reactive lipid aldehydes and protein carbonylation by glutathionylation using glutathione-S-transferase A4 (GSTA4) or carbonyl reduction/oxidation via reductases and/or dehydrogenases. Insulin resistance in mice is linked to ROS production and increased level of protein carbonylation, mitochondrial dysfunction, decreased insulin-stimulated glucose transport, and altered adipokine secretion. To assess protein carbonylation and insulin resistance in humans, eight healthy participants underwent subcutaneous fat biopsy from the periumbilical region for protein analysis and frequently sampled intravenous glucose tolerance testing to measure insulin sensitivity. Soluble proteins from adipose tissue were analyzed using two-dimensional gel electrophoresis and the major carbonylated proteins identified as the adipocyte and epithelial fatty acid-binding proteins. The level of protein carbonylation was directly correlated with adiposity and serum free fatty acids (FFAs). These results suggest that in human obesity oxidative stress is linked to protein carbonylation and such events may contribute to the development of insulin resistance.
authors: Division of Pediatric Endocrinology, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Brigitte I
authors: BI
authors: Frohnert
authors: Alan R
authors: AR
authors: Sinaiko
authors: Federico J
authors: FJ
authors: Serrot
authors: Rocio E
authors: RE
authors: Foncea
authors: Antoinette
authors: A
authors: Moran
authors: Sayeed
authors: S
authors: Ikramuddin
authors: Umar
authors: U
authors: Choudry
authors: David A
authors: DA
authors: Bernlohr
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