JNK and Tumor Necrosis Factor-α Mediate Free Fatty Acid-induced Insulin Resistance in 3T3-L1 Adipocytes

摘要: Lipid infusion and high fat feeding are established causes of systemic adipose tissue insulin resistance. In this study, we treated 3T3-L1 adipocytes with a mixture free fatty acids (FFAs) to investigate the molecular mechanisms underlying fat-induced FFA treatment impaired receptor-mediated signal transduction decreased insulin-stimulated GLUT4 translocation glucose transport. FFAs activated stress/inflammatory kinases c-Jun N-terminal kinase (JNK) IKKbeta, suppressor cytokine signaling protein 3, increased secretion inflammatory tumor necrosis factor (TNF)-alpha, adiponectin into medium. RNA interference-mediated down-regulation JNK blocked activation prevented most FFA-induced defects in action. Blockade TNF-alpha neutralizing antibodies or its receptors dominant negative peptide had partial effect inhibit cellular We found that by was not inhibited blocking signaling, whereas increase knockdown. Together, these results indicate 1) can be through TNF-alpha-independent mechanisms, 2) is major contributor resistance, 3) an autocrine/paracrine downstream effector also mediate