title: Implication of inflammatory signaling pathways in obesity-induced insulin resistance.
abstract: Obesity is characterized by the development of a low-grade chronic inflammatory state in different metabolic tissues including adipose tissue and liver. This inflammation develops in response to an excess of nutrient flux and is now recognized as an important link between obesity and insulin resistance. Several dietary factors like saturated fatty acids and glucose as well as changes in gut microbiota have been proposed as triggers of this metabolic inflammation through the activation of pattern-recognition receptors (PRRs), including Toll-like receptors (TLR), inflammasome, and nucleotide oligomerization domain (NOD). The consequences are the production of pro-inflammatory cytokines and the recruitment of immune cells such as macrophages and T lymphocytes in metabolic tissues. Inflammatory cytokines activate several kinases like IKKβ, mTOR/S6 kinase, and MAP kinases as well as SOCS proteins that interfere with insulin signaling and action in adipocytes and hepatocytes. In this review, we summarize recent studies demonstrating that PRRs and stress kinases are important integrators of metabolic and inflammatory stress signals in metabolic tissues leading to peripheral and central insulin resistance and metabolic dysfunction. We discuss recent data obtained with genetically modified mice and pharmacological approaches suggesting that these inflammatory pathways are potential novel pharmacological targets for the management of obesity-associated insulin resistance.
authors: INSERM U1065, Mediterranean Center of Molecular Medicine (C3M), Team "Molecular and Cellular Physiopathology of Obesity and Diabetes" Nice, France ; Faculty of Medicine, University of Nice Sophia-Antipolis Nice, France.
authors: Jean-François
authors: JF
authors: Tanti
authors: Franck
authors: F
authors: Ceppo
authors: Jennifer
authors: J
authors: Jager
authors: Flavien
authors: F
authors: Berthou
keywords: adipose tissue; inflammation; insulin resistance; macrophages; obesity; pattern-recognition receptors; stress kinases