- Taniguchi, C.M., Emanuelli, B. & Kahn, C.R. Critical nodes in signalling pathways: insights into insulin action. Nat. Rev. Mol. Cell Biol. 7, 85–96 (2006).
Article CAS PubMed Google Scholar
- Reaven, G.M. The insulin resistance syndrome: definition and dietary approaches to treatment. Annu. Rev. Nutr. 25, 391–406 (2005).
Article CAS PubMed Google Scholar
- Reaven, G.M. Why Syndrome X? From Harold Himsworth to the insulin resistance syndrome. Cell Metab. 1, 9–14 (2005).
Article CAS PubMed Google Scholar
- Stumvoll, M., Goldstein, B.J. & van Haeften, T.W. Type 2 diabetes: principles of pathogenesis and therapy. Lancet 365, 1333–1346 (2005).
Article CAS PubMed Google Scholar
- Biddinger, S.B. & Kahn, C.R. From mice to men: insights into the insulin resistance syndromes. Annu. Rev. Physiol. 68, 123–158 (2006).
Article CAS PubMed Google Scholar
- Doria, A., Patti, M.E. & Kahn, C.R. The emerging genetic architecture of type 2 diabetes. Cell Metab. 8, 186–200 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Olefsky, J.M. & Glass, C.K. Macrophages, inflammation, and insulin resistance. Annu. Rev. Physiol. 72, 219–246 (2010).
Article CAS PubMed Google Scholar
- Li, P. et al. Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice. J. Biol. Chem. 285, 15333–15345 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Lumeng, C.N. & Saltiel, A.R. Inflammatory links between obesity and metabolic disease. J. Clin. Invest. 121, 2111–2117 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Gregor, M.F. & Hotamisligil, G.S. Inflammatory mechanisms in obesity. Annu. Rev. Immunol. 29, 415–445 (2011).
Article CAS PubMed Google Scholar
- Hotamisligil, G.S. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140, 900–917 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Wunderlich, F.T. et al. Hepatic NF-κB essential modulator deficiency prevents obesity-induced insulin resistance but synergizes with high-fat feeding in tumorigenesis. Proc. Natl. Acad. Sci. USA 105, 1297–1302 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Arkan, M.C. et al. IKK-β links inflammation to obesity-induced insulin resistance. Nat. Med. 11, 191–198 (2005).
Article CAS PubMed Google Scholar
- Goldfine, A.B. et al. The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann. Intern. Med. 152, 346–357 (2010).
Article PubMed PubMed Central Google Scholar
- Chiang, S.H. et al. The protein kinase IKKɛ regulates energy balance in obese mice. Cell 138, 961–975 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Chau, T.L. et al. Are the IKKs and IKK-related kinases TBK1 and IKK-epsilon similarly activated? Trends Biochem. Sci. 33, 171–180 (2008).
Article CAS PubMed Google Scholar
- Chariot, A. The NF-κB–independent functions of IKK subunits in immunity and cancer. Trends Cell Biol. 19, 404–413 (2009).
Article CAS PubMed Google Scholar
- Kawai, T. & Akira, S. Signaling to NF-κB by Toll-like receptors. Trends Mol. Med. 13, 460–469 (2007).
Article CAS PubMed Google Scholar
- Kravchenko, V.V., Mathison, J.C., Schwamborn, K., Mercurio, F. & Ulevitch, R.J. IKKi/IKKɛ plays a key role in integrating signals induced by pro-inflammatory stimuli. J. Biol. Chem. 278, 26612–26619 (2003).
Article CAS PubMed Google Scholar
- Makino, H., Saijo, T., Ashida, Y., Kuriki, H. & Maki, Y. Mechanism of action of an antiallergic agent, amlexanox (AA-673), in inhibiting histamine release from mast cells. Acceleration of cAMP generation and inhibition of phosphodiesterase. Int. Arch. Allergy Appl. Immunol. 82, 66–71 (1987).
Article CAS PubMed Google Scholar
- Bell, J. Amlexanox for the treatment of recurrent aphthous ulcers. Clin. Drug Investig. 25, 555–566 (2005).
Article CAS PubMed Google Scholar
- Saltiel, A.R. Insulin resistance in the defense against obesity. Cell Metab. 15, 798–804 (2012).
Article CAS PubMed Google Scholar
- Lumeng, C.N., Deyoung, S.M. & Saltiel, A.R. Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins. Am. J. Physiol. Endocrinol. Metab. 292, E166–E174 (2007).
Article CAS PubMed Google Scholar
- Karin, M., Yamamoto, Y. & Wang, Q.M. The IKK NF-κB system: a treasure trove for drug development. Nat. Rev. Drug Discov. 3, 17–26 (2004).
Article CAS PubMed Google Scholar
- Oh, D.Y. et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142, 687–698 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Ma, X. et al. Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation. Proc. Natl. Acad. Sci. USA 109, 9378–9383 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Clark, K., Takeuchi, O., Akira, S. & Cohen, P. The TRAF-associated protein TANK facilitates cross-talk within the IκB kinase family during Toll-like receptor signaling. Proc. Natl. Acad. Sci. USA 108, 17093–17098 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Bamborough, P. et al. 5-(1H-Benzimidazol-1-yl)-3-alkoxy-2-thiophenecarbonitriles as potent, selective, inhibitors of IKK-ɛn kinase. Bioorg. Med. Chem. Lett. 16, 6236–6240 (2006).
Article CAS PubMed Google Scholar
- Clark, K. et al. Novel cross-talk within the IKK family controls innate immunity. Biochem. J. 434, 93–104 (2011).
Article CAS PubMed Google Scholar
- Torii, H. et al. Metabolic fate of amoxanox (AA-673), a new antiallergic agent, in rats, mice, guinea-pigs and dogs. Jpn. Pharmacol. Ther. 13, 4933–4954 (1985).
CAS Google Scholar
- Friedman, J.M. Modern science versus the stigma of obesity. Nat. Med. 10, 563–569 (2004).
Article CAS PubMed Google Scholar
- Friedman, J.M. & Halaas, J.L. Leptin and the regulation of body weight in mammals. Nature 395, 763–770 (1998).
Article CAS PubMed Google Scholar
- Weisberg, S.P. et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796–1808 (2003).
Article CAS PubMed PubMed Central Google Scholar
- Lumeng, C.N., Bodzin, J.L. & Saltiel, A.R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117, 175–184 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Um, S.H. et al. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 431, 200–205 (2004).
Article CAS PubMed Google Scholar
- Seals, D.R. & Bell, C. Chronic sympathetic activation: consequence and cause of age-associated obesity? Diabetes 53, 276–284 (2004).
Article CAS PubMed Google Scholar
- Olefsky, J.M. & Saltiel, A.R. PPARγ and the treatment of insulin resistance. Trends Endocrinol. Metab. 11, 362–368 (2000).
Article CAS PubMed Google Scholar
- Pradhan, A.D., Manson, J.E., Rifai, N., Buring, J.E. & Ridker, P.M. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. J. Am. Med. Assoc. 286, 327–334 (2001).
Article CAS Google Scholar
- Festa, A., D′Agostino, R. Jr., Tracy, R.P. & Haffner, S.M. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51, 1131–1137 (2002).
Article CAS PubMed Google Scholar
- Blackburn, P. et al. Postprandial variations of plasma inflammatory markers in abdominally obese men. Obesity (Silver Spring) 14, 1747–1754 (2006).
Article CAS Google Scholar
- Aron-Wisnewsky, J. et al. Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J. Clin. Endocrinol. Metab. 94, 4619–4623 (2009).
Article CAS PubMed Google Scholar
- Schenk, S., Saberi, M. & Olefsky, J.M. Insulin sensitivity: modulation by nutrients and inflammation. J. Clin. Invest. 118, 2992–3002 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Odegaard, J.I. & Chawla, A. Alternative macrophage activation and metabolism. Annu. Rev. Pathol. 6, 275–297 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Nishimura, S. et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat. Med. 15, 914–920 (2009).
Article CAS PubMed Google Scholar
- Winer, S. et al. Normalization of obesity-associated insulin resistance through immunotherapy. Nat. Med. 15, 921–929 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Feuerer, M. et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat. Med. 15, 930–939 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Winer, D.A. et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat. Med. 17, 610–617 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Nakamura, T. et al. Double-stranded RNA–dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell 140, 338–348 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Summers, S.A. Sphingolipids and insulin resistance: the five Ws. Curr. Opin. Lipidol. 21, 128–135 (2010).
Article CAS PubMed Google Scholar
- Vandanmagsar, B. et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 17, 179–188 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Saberi, M. et al. Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat–fed mice. Cell Metab. 10, 419–429 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Wellen, K.E. et al. Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis. Cell 129, 537–548 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Lesniewski, L.A. et al. Bone marrow–specific Cap gene deletion protects against high-fat diet–induced insulin resistance. Nat. Med. 13, 455–462 (2007).
Article CAS PubMed Google Scholar
- Holland, W.L. et al. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab. 5, 167–179 (2007).
Article CAS PubMed Google Scholar
- Shi, H. et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116, 3015–3025 (2006).
Article CAS PubMed PubMed Central Google Scholar
- Solomon, D.H. et al. Association between disease-modifying antirheumatic drugs and diabetes risk in patients with rheumatoid arthritis and psoriasis. J. Am. Med. Assoc. 305, 2525–2531 (2011).
Article CAS Google Scholar
- Hundal, R.S. et al. Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J. Clin. Invest. 109, 1321–1326 (2002).
Article CAS PubMed PubMed Central Google Scholar
- Zhang, X. et al. Selective inactivation of c-Jun NH2-terminal kinase in adipose tissue protects against diet-induced obesity and improves insulin sensitivity in both liver and skeletal muscle in mice. Diabetes 60, 486–495 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Liu, J. et al. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat. Med. 15, 940–945 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Zick, Y. Ser/Thr phosphorylation of IRS proteins: a molecular basis for insulin resistance. Sci. STKE 2005, pe4 (2005).
Article PubMed Google Scholar