proteasome dysfunction associated to oxidative stress and proteotoxicity in adipocytes compromises insulin sensitivity in human obesity：蛋白酶体功能障碍在脂肪细胞的胰岛素敏感性在人类肥胖的妥协和氧化应激蛋白毒性作用有关.pdf

ANTIOXIDANTS REDOX SIGNALING Volume 23, Number 7, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/ars.2014.5939 ORIGINAL RESEARCH COMMUNICATION Proteasome Dysfunction Associated to Oxidative Stress and Proteotoxicity in Adipocytes Compromises Insulin Sensitivity in Human Obesity 1,2,* 1,2,* 1,2 2,3 Alberto Dı´az-Ruiz, Rocı´o Guzma´n-Ruiz, Natalia R. Moreno, Antonio Garcı´a-Rios, 2,3 4 5 2,6 Nieves Delgado-Casado, Antonio Membrives, Isaac Tu´ nez, Rajaa El Bekay, 2,7 2,8 2,8 2,6 Jose´ M. Ferna´ ndez-Real, Sulay Tovar, Carlos Die´ guez, Francisco J. Tinahones, 1,2 2,3 1,2 Rafael Va´ zquez-Martı´nez, Jose´ Lo´ pez-Miranda, and Marı´a M. Malago´ n Abstract Aims: Obesity is characterized by a low-grade systemic inflammatory state and adipose tissue (AT) dysfunc- tion, which predispose individuals to the development of insulin resistance (IR) and metabolic disease. How- ever, a subset of obese individuals, referred to as metabolically healthy obese (MHO) individuals, are protected from obesity-associated metabolic abnormalities. Here, we aim at identifying molecular factors and pathways in adipocytes that are responsible for the progression from the insulin-sensitive to the insulin-resistant, meta- bolically unhealthy obese (MUHO) phenotype. Results: Proteomic analysis of paired samples of adipocytes from subcutaneous (SC) and omental (OM) human AT revealed that both types of cells are altered in the MUHO state. Specifi