HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hotamisligil, G. S. Search for Related Content PubMed PubMed Citation Articles by Hotamisligil, G. S. Social Bookmarking                What's this?

Role of Endoplasmic Reticulum Stress and c-Jun NH₂-Terminal Kinase Pathways in Inflammation and Origin of Obesity and Diabetes

From the Departments of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts

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)- 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-B 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.

Abbreviations: ER, endoplasmic reticulum; IKK, inhibitor of nuclear factor-B kinase; IRS, insulin receptor substrate; JIP, JNK-interacting protein; JNK, c-Jun NH₂ terminal kinase; TNF, tumor necrosis factor

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Xu, A. W.K. Tso, B. M.Y. Cheung, Y. Wang, N. M.S. Wat, C. H.Y. Fong, D. C.Y. Yeung, E. D. Janus, P. C. Sham, and K. S.L. Lam Circulating Adipocyte-Fatty Acid Binding Protein Levels Predict the Development of the Metabolic Syndrome: A 5-Year Prospective Study Circulation, March 27, 2007; 115(12): 1537 - 1543. [Abstract] [Full Text] [PDF]

				M. A. Bogoyevitch and B. Kobe Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases Microbiol. Mol. Biol. Rev., December 1, 2006; 70(4): 1061 - 1095. [Abstract] [Full Text] [PDF]

				T. Alquier, C. Leloup, A. Lorsignol, and L. Penicaud Translocable Glucose Transporters in the Brain: Where Are We in 2006? Diabetes, December 1, 2006; 55(Supplement_2): S131 - S138. [Abstract] [Full Text] [PDF]

				T. TELI, D. XANTHAKI, and K. P KARALIS Regulation of Appetite and Insulin Signaling in Inflammatory States Ann. N.Y. Acad. Sci., November 1, 2006; 1083(1): 319 - 328. [Abstract] [Full Text] [PDF]

				G. Tuncman, J. Hirosumi, G. Solinas, L. Chang, M. Karin, and G. S. Hotamisligil Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance PNAS, July 11, 2006; 103(28): 10741 - 10746. [Abstract] [Full Text] [PDF]

				D. Mozaffarian, M. B. Katan, A. Ascherio, M. J. Stampfer, and W. C. Willett Trans Fatty Acids and Cardiovascular Disease N. Engl. J. Med., April 13, 2006; 354(15): 1601 - 1613. [Full Text] [PDF]