title: Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes.
abstract: Metabolic and immune systems are the most fundamental requirements for survival, and many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily highly conserved. Consequently, metabolic and immune pathways are also highly integrated and interdependent. In the past decade, it became apparent that this interface plays a critical role in the pathogenesis of chronic metabolic diseases, particularly obesity and type 2 diabetes. Importantly, the inflammatory component in obesity and diabetes is now firmly established with the discovery of causal links between inflammatory mediators, such as tumor necrosis factor (TNF)-alpha and insulin receptor signaling and the elucidation of the underlying molecular mechanisms, such as c-Jun NH2-terminal kinase (JNK)- and inhibitor of nuclear factor-kappaB kinase-mediated transcriptional and posttranslational modifications that inhibit insulin action. More recently, obesity-induced endoplasmic reticulum stress has been demonstrated to underlie the initiation of obesity-induced JNK activation, inflammatory responses, and generation of peripheral insulin resistance. This article will review the link between stress, inflammation, and metabolic disease, particularly type 2 diabetes, and discuss the mechanistic and therapeutic opportunities that emerge from this platform by focusing on JNK and endoplasmic reticulum stress responses.
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, USA. ghotamis@hsph.harvard.edu
authors.forename: Gökhan S
authors.initials: GS
authors.lastname: Hotamisligil
mesh_terms: D003920:Diabetes Mellitus / Q000503:physiopathology*; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D009765:Obesity / Q000503:physiopathology*; D013312:Stress, Physiological
chemical_list: D007328:Insulin; D048031:JNK Mitogen-Activated Protein Kinases