Stevens, G.A. et al. National, regional, and global trends in adult overweight and obesity prevalences. Popul. Health Metr. 10, 22 (2012).
Danaei, G. et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 378, 31–40 (2011).
Xu, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112, 1821–1830 (2003).
Weisberg, S.P. et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796–1808 (2003).
Hotamisligil, G.S. Inflammation and metabolic disorders. Nature 444, 860–867 (2006).
Lynch, L. et al. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 37, 574–587 (2012).
Molofsky, A.B. et al. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J. Exp. Med. 210, 535–549 (2013).
Schipper, H.S. et al. Natural killer T cells in adipose tissue prevent insulin resistance. J. Clin. Invest. 122, 3343–3354 (2012).
Wu, D. et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332, 243–247 (2011).
Cao, H. Adipocytokines in obesity and metabolic disease. J. Endocrinol. 220, T47–T59 (2014).
Shi, H. et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116, 3015–3025 (2006).
Ye, J., Gao, Z., Yin, J. & He, Q. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am. J. Physiol. Endocrinol. Metab. 293, E1118–E1128 (2007).
Khan, T. et al. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol. Cell. Biol. 29, 1575–1591 (2009).
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).
Talukdar, S. et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat. Med. 18, 1407–1412 (2012).
Nishimura, S. et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat. Med. 15, 914–920 (2009).
Borst, S.E. The role of TNF-alpha in insulin resistance. Endocrine 23, 177–182 (2004).
Patsouris, D. et al. Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab. 8, 301–309 (2008).
Vivier, E. et al. Innate or adaptive immunity? The example of natural killer cells. Science 331, 44–49 (2011).
Shi, F.D., Ljunggren, H.G., La Cava, A. & Van Kaer, L. Organ-specific features of natural killer cells. Nat. Rev. Immunol. 11, 658–671 (2011).
Gazit, R. et al. Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1. Nat. Immunol. 7, 517–523 (2006).
Gur, C. et al. The activating receptor NKp46 is essential for the development of type 1 diabetes. Nat. Immunol. 11, 121–128 (2010).
Mosser, D.M. & Edwards, J.P. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8, 958–969 (2008).
Goldszmid, R.S. et al. NK cell-derived interferon-gamma orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infection. Immunity 36, 1047–1059 (2012).
Han, M.S. et al. JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. Science 339, 218–222 (2013).
O'Rourke, R.W. et al. Systemic inflammation and insulin sensitivity in obese IFN-gamma knockout mice. Metabolism 61, 1152–1161 (2012).
Wong, N. et al. Deficiency in interferon-gamma results in reduced body weight and better glucose tolerance in mice. Endocrinology 152, 3690–3699 (2011).
Rocha, V.Z. et al. Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circ. Res. 103, 467–476 (2008).
Hayakawa, Y. & Smyth, M.J. CD27 dissects mature NK cells into two subsets with distinct responsiveness and migratory capacity. J. Immunol. 176, 1517–1524 (2006).
Klose, C.S. et al. Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell 157, 340–356 (2014).
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).
Waggoner, S.N., Cornberg, M., Selin, L.K. & Welsh, R.M. Natural killer cells act as rheostats modulating antiviral T cells. Nature 481, 394–398 (2012).
Feng, B. et al. Clodronate liposomes improve metabolic profile and reduce visceral adipose macrophage content in diet-induced obese mice. PLoS ONE 6, e24358 (2011).
Blunt, T. et al. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. Cell 80, 813–823 (1995).
Wong, R.H. et al. A role of DNA-PK for the metabolic gene regulation in response to insulin. Cell 136, 1056–1072 (2009).
Ballak, D.B. et al. Combined B- and T-cell deficiency does not protect against obesity-induced glucose intolerance and inflammation. Cytokine 62, 96–103 (2013).
Amano, S.U. et al. Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab. 19, 162–171 (2014).
Zafirova, B., Wensveen, F.M., Gulin, M. & Polic, B. Regulation of immune cell function and differentiation by the NKG2D receptor. Cell. Mol. Life Sci. 68, 3519–3529 (2011).
Inzucchi, S.E. et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 55, 1577–1596 (2012).
Johnson, A.R., Milner, J.J. & Makowski, L. The inflammation highway: metabolism accelerates inflammatory traffic in obesity. Immunol. Rev. 249, 218–238 (2012).
Ozcan, U. et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306, 457–461 (2004).
Houstis, N., Rosen, E.D. & Lander, E.S. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440, 944–948 (2006).
Haus, J.M. et al. Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes 58, 337–343 (2009).
Aouadi, M. et al. Gene silencing in adipose tissue macrophages regulates whole-body metabolism in obese mice. Proc. Natl. Acad. Sci. USA 110, 8278–8283 (2013).
Tripp, C.S., Wolf, S.F. & Unanue, E.R. Interleukin 12 and tumor necrosis factor alpha are costimulators of interferon gamma production by natural killer cells in severe combined immunodeficiency mice with listeriosis, and interleukin 10 is a physiologic antagonist. Proc. Natl. Acad. Sci. USA 90, 3725–3729 (1993).
Bryceson, Y.T., March, M.E., Ljunggren, H.G. & Long, E.O. Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion. Blood 107, 159–166 (2006).
Ouchi, N., Parker, J.L., Lugus, J.J. & Walsh, K. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 11, 85–97 (2011).
Wang, Q.A., Tao, C., Gupta, R.K. & Scherer, P.E. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat. Med. 19, 1338–1344 (2013).
Huebner, L. et al. Human NK cell subset functions are differentially affected by adipokines. PLoS ONE 8, e75703 (2013).
Polić, B. et al. Hierarchical and redundant lymphocyte subset control precludes cytomegalovirus replication during latent infection. J. Exp. Med. 188, 1047–1054 (1998).