Affiliation:
1. From the Departments of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts
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)-α 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-κB 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.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
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