Louie, J. K. et al. A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin. Infect. Dis. 52, 301–312 (2011).
Sattar, N., McInnes, I. B. & McMurray, J. J. V. Obesity is a risk factor for severe COVID-19 infection: multiple potential mechanisms. Circulation 142, 4–6 (2020).
Hamer, M., Gale, C. R., Kivimäki, M. & Batty, G. D. Overweight, obesity, and risk of hospitalization for COVID-19: a community-based cohort study of adults in the United Kingdom. Proc. Natl Acad. Sci. USA 117, 21011–21013 (2020).
Maurya, R., Sebastian, P., Namdeo, M., Devender, M. & Gertler, A. COVID-19 severity in obesity: leptin and inflammatory cytokine interplay in the link between high morbidity and mortality. Front. Immunol. 12, 649359 (2021).
Rebello, C. J., Kirwan, J. P. & Greenway, F. L. Obesity, the most common comorbidity in SARS-CoV-2: is leptin the link? Int. J. Obes. 44, 1810–1817 (2020).
Guo, S. A. et al. Obesity is associated with attenuated tissue immunity in COVID-19. Am. J. Respir. Crit. Care Med. 207, 566–576 (2023).
Shaikh, S. R., Beck, M. A., Alwarawrah, Y. & MacIver, N. J. Emerging mechanisms of obesity-associated immune dysfunction. Nat. Rev. Endocrinol. 20, 136–148 (2024).
McKay, R. M., McKay, J. P., Avery, L. & Graff, J. M. C. elegans: a model for exploring the genetics of fat storage. Dev. Cell 4, 131–142 (2003).
Agrawal, N. et al. The Drosophila TNF Eiger is an adipokine that acts on insulin-producing cells to mediate nutrient response. Cell Metab. 23, 675–684 (2016).
Chang, C. H. et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153, 1239–1251 (2013).
Newsholme, P., Gordon, S. & Newsholme, E. A. Rates of utilization and fates of glucose, glutamine, pyruvate, fatty acids and ketone bodies by mouse macrophages. Biochem. J. 242, 631–636 (1987).
Krawczyk, C. M. et al. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 115, 4742–4749 (2010).
Huang, S. C. et al. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat. Immunol. 15, 846–855 (2014).
Kent, S., Bluthé, R. M., Kelley, K. W. & Dantzer, R. Sickness behavior as a new target for drug development. Trends Pharmacol. Sci. 13, 24–28 (1992).
Grant, R. W. & Stephens, J. M. Fat in flames: influence of cytokines and pattern recognition receptors on adipocyte lipolysis. Am. J. Physiol. Endocrinol. Metab. 309, E205–E213 (2015).
Zimmermann, R. et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306, 1383–1386 (2004).
Fruhbeck, G., Mendez-Gimenez, L., Fernandez-Formoso, J. A., Fernandez, S. & Rodriguez, A. Regulation of adipocyte lipolysis. Nutr. Res. Rev. 27, 63–93 (2014).
Friedman, J. M. Leptin and the endocrine control of energy balance. Nat. Metab. 1, 754–764 (2019).
Dallner, O. S. et al. Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity. Nat. Med. 25, 507–516 (2019).
Saladin, R. et al. Transient increase in obese gene expression after food intake or insulin administration. Nature 377, 527–529 (1995).
Kirchgessner, T. G., Uysal, K. T., Wiesbrock, S. M., Marino, M. W. & Hotamisligil, G. S. Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes. J. Clin. Invest. 100, 2777–2782 (1997).
Saucillo, D. C., Gerriets, V. A., Sheng, J., Rathmell, J. C. & Maciver, N. J. Leptin metabolically licenses T cells for activation to link nutrition and immunity. J. Immunol. 192, 136–144 (2014).
Balthasar, N. et al. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123, 493–505 (2005).
Rossi, J. et al. Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metab. 13, 195–204 (2011).
Sohn, J. W. et al. Melanocortin 4 receptors reciprocally regulate sympathetic and parasympathetic preganglionic neurons. Cell 152, 612–619 (2013).
Catania, A., Gatti, S., Colombo, G. & Lipton, J. M. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol. Rev. 56, 1–29 (2004).
Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994).
Bjorbak, C. et al. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J. Biol. Chem. 275, 40649–40657 (2000).
Considine, R. V. et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 334, 292–295 (1996).
Schwartz, M. W., Woods, S. C., Porte, D. Jr, Seeley, R. J. & Baskin, D. G. Central nervous system control of food intake. Nature 404, 661–671 (2000).
Kershaw, E. E. & Flier, J. S. Adipose tissue as an endocrine organ. J. Clin. Endocrinol. Metab. 89, 2548–2556 (2004).
Zhang, F. et al. Crystal structure of the obese protein leptin-E100. Nature 387, 206–209 (1997).
Faggioni, R. et al. IL-1 beta mediates leptin induction during inflammation. Am. J. Physiol. 274, R204–R208 (1998).
Procaccini, C., Jirillo, E. & Matarese, G. Leptin as an immunomodulator. Mol. Asp. Med. 33, 35–45 (2012).
Caldefie-Chezet, F., Poulin, A. & Vasson, M. P. Leptin regulates functional capacities of polymorphonuclear neutrophils. Free Radic. Res. 37, 809–814 (2003).
Tian, Z., Sun, R., Wei, H. & Gao, B. Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation. Biochem. Biophys. Res. Commun. 298, 297–302 (2002).
Lord, G. M. et al. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394, 897–901 (1998).
Banks, W. A., DiPalma, C. R. & Farrell, C. L. Impaired transport of leptin across the blood–brain barrier in obesity. Peptides 20, 1341–1345 (1999).
El-Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjørbaek, C. & Flier, J. S. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J. Clin. Invest. 105, 1827–1832 (2000).
Van Heek, M. et al. Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J. Clin. Invest. 99, 385–390 (1997).
Barr, V. A., Lane, K. & Taylor, S. I. Subcellular localization and internalization of the four human leptin receptor isoforms. J. Biol. Chem. 274, 21416–21424 (1999).
Seo, S. et al. Requirement of Bardet–Biedl syndrome proteins for leptin receptor signaling. Hum. Mol. Genet. 18, 1323–1331 (2009).
Knight, Z. A., Hannan, K. S., Greenberg, M. L. & Friedman, J. M. Hyperleptinemia is required for the development of leptin resistance. PLoS ONE 5, e11376 (2010).
Ernst, M. B. et al. Enhanced Stat3 activation in POMC neurons provokes negative feedback inhibition of leptin and insulin signaling in obesity. J. Neurosci. 29, 11582–11593 (2009).
Tam, J. et al. Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance. Cell Metab. 16, 167–179 (2012).
Zhao, S. et al. Partial leptin reduction as an insulin sensitization and weight loss strategy. Cell Metab. 30, 706–719.e6 (2019).
Milanski, M. et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J. Neurosci. 29, 359–370 (2009).
Howard, J. K. et al. Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J. Clin. Invest. 104, 1051–1059 (1999).
Tschop, J. et al. CNS leptin action modulates immune response and survival in sepsis. J. Neurosci. 30, 6036–6047 (2010).
Mancuso, P. et al. Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia. J. Immunol. 168, 4018–4024 (2002).
Mancuso, P., Huffnagle, G. B., Olszewski, M. A., Phipps, J. & Peters-Golden, M. Leptin corrects host defense defects after acute starvation in murine pneumococcal pneumonia. Am. J. Respir. Crit. Care Med. 173, 212–218 (2006).
Radigan, K. A. et al. Impaired clearance of influenza A virus in obese, leptin receptor deficient mice is independent of leptin signaling in the lung epithelium and macrophages. PLoS ONE 9, e108138 (2014).
Zhang, A. J. X. et al. Leptin mediates the pathogenesis of severe 2009 pandemic influenza A(H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity. J. Infect. Dis. 207, 1270–1280 (2013).
Matarese, G. et al. Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells. Proc. Natl Acad. Sci. USA 102, 5150–5155 (2005).
De Rosa, V. et al. A key role of leptin in the control of regulatory T cell proliferation. Immunity 26, 241–255 (2007).
Gerriets, V. A. et al. Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity. Eur. J. Immunol. 46, 1970–1983 (2016).
Kiernan, K., Nichols, A. G., Alwarawrah, Y. & MacIver, N. J. Effects of T cell leptin signaling on systemic glucose tolerance and T cell responses in obesity. PLoS ONE 18, e0286470 (2023).
Hsu, A., Aronoff, D. M., Phipps, J., Goel, D. & Mancuso, P. Leptin improves pulmonary bacterial clearance and survival in ob/ob mice during pneumococcal pneumonia. Clin. Exp. Immunol. 150, 332–339 (2007).
Faggioni, R. et al. Leptin deficiency enhances sensitivity to endotoxin-induced lethality. Am. J. Physiol. 276, R136–R142 (1999).
Takahashi, N., Waelput, W. & Guisez, Y. Leptin is an endogenous protective protein against the toxicity exerted by tumor necrosis factor. J. Exp. Med. 189, 207–212 (1999).
Schwartz, M. W., Seeley, R. J., Campfield, L. A., Burn, P. & Baskin, D. G. Identification of targets of leptin action in rat hypothalamus. J. Clin. Invest. 98, 1101–1106 (1996).
Cheung, C. C., Clifton, D. K. & Steiner, R. A. Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138, 4489–4492 (1997).
Williams, K. W. et al. Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. J. Neurosci. 30, 2472–2479 (2010).
Elias, C. F. et al. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 23, 775–786 (1999).
Berglund, E. D. et al. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J. Clin. Invest. 122, 1000–1009 (2012).
Vong, L. et al. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71, 142–154 (2011).
Yeo, G. S. H. et al. The melanocortin pathway and energy homeostasis: from discovery to obesity therapy. Mol. Metab. 48, 101206 (2021).
Lindberg, I. & Fricker, L. D. Obesity, POMC, and POMC-processing enzymes: surprising results from animal models. Endocrinology 162, bqab155 (2021).
Dowsett, G. K. C. et al. A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing. Mol. Metab. 53, 101240 (2021).
Mountjoy, K. G., Robbins, L. S., Mortrud, M. T. & Cone, R. D. The cloning of a family of genes that encode the melanocortin receptors. Science 257, 1248–1251 (1992).
Cone, R. D. Studies on the physiological functions of the melanocortin system. Endocr. Rev. 27, 736–749 (2006).
Laiho, L. & Murray, J. F. The multifaceted melanocortin receptors. Endocrinology 163, bqac083 (2022).
Lu, D. et al. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 371, 799–802 (1994).
Gantz, I. et al. Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J. Biol. Chem. 268, 15174–15179 (1993).
Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B. & Cone, R. D. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol. Endocrinol. 8, 1298–1308 (1994).
Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J. & Cone, R. D. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385, 165–168 (1997).
Georgescu, T. et al. Neurochemical characterization of brainstem pro-opiomelanocortin cells. Endocrinology 161, bqaa032 (2020).
Lipton, J. M. & Glyn, J. R. Central administration of peptides alters thermoregulation in the rabbit. Peptides 1, 15–18 (1980).
Glyn, J. R. & Lipton, J. M. Hypothermic and antipyretic effects of centrally administered ACTH (1–24) and alpha-melanotropin. Peptides 2, 177–187 (1981).
Delgado Hernandez, R. et al. Inhibition of systemic inflammation by central action of the neuropeptide alpha-melanocyte-stimulating hormone. Neuroimmunomodulation 6, 187–192 (1999).
Ceriani, G., Macaluso, A., Catania, A. & Lipton, J. M. Central neurogenic antiinflammatory action of alpha-MSH: modulation of peripheral inflammation induced by cytokines and other mediators of inflammation. Neuroendocrinology 59, 138–143 (1994).
Lipton, J. M., Macaluso, A., Hiltz, M. E. & Catania, A. Central administration of the peptide alpha-MSH inhibits inflammation in the skin. Peptides 12, 795–798 (1991).
Macaluso, A. et al. Antiinflammatory influences of alpha-MSH molecules: central neurogenic and peripheral actions. J. Neurosci. 14, 2377–2382 (1994).
Mountjoy, K. G. et al. Desacetyl-alpha-melanocyte stimulating hormone and alpha-melanocyte stimulating hormone are required to regulate energy balance. Mol. Metab. 9, 207–216 (2018).
Reynolds, R. P. et al. Alpha-melanocyte-stimulating hormone contributes to an anti-inflammatory response to lipopolysaccharide. Mol. Metab. 87, 101986 (2024).
Wang, W., Guo, D. Y., Lin, Y. J. & Tao, Y. X. Melanocortin regulation of inflammation. Front. Endocrinol. 10, 683 (2019).
Getting, S. J., Christian, H. C., Flower, R. J. & Perretti, M. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis. Arthritis Rheum. 46, 2765–2775 (2002).
Taherzadeh, S. et al. alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages. Am. J. Physiol. 276, R1289–R1294 (1999).
Star, R. A. et al. Evidence of autocrine modulation of macrophage nitric oxide synthase by alpha-melanocyte-stimulating hormone. Proc. Natl Acad. Sci. USA 92, 8016–8020 (1995).
Catania, A. et al. The neuropeptide alpha-MSH has specific receptors on neutrophils and reduces chemotaxis in vitro. Peptides 17, 675–679 (1996).
Colombo, G. et al. Production and effects of alpha-melanocyte-stimulating hormone during acute lung injury. Shock 27, 326–333 (2007).
Getting, S. J. et al. A role for MC3R in modulating lung inflammation. Pulm. Pharmacol. Ther. 21, 866–873 (2008).
Vulliemoz, N. R., Xiao, E., Xia-Zhang, L., Ferin, M. & Wardlaw, S. L. Melanocortin modulation of inflammatory cytokine and neuroendocrine responses to endotoxin in the monkey. Endocrinology 147, 1878–1883 (2006).
Li, M. M. et al. The paraventricular hypothalamus regulates satiety and prevents obesity via two genetically distinct circuits. Neuron 102, 653–667.e6 (2019).
Andersen, G. N. et al. Quantitative measurement of the levels of melanocortin receptor subtype 1, 2, 3 and 5 and pro-opio-melanocortin peptide gene expression in subsets of human peripheral blood leucocytes. Scand. J. Immunol. 61, 279–284 (2005).
Xu, Y. et al. Pituitary hormone alpha-MSH promotes tumor-induced myelopoiesis and immunosuppression. Science 377, 1085–1091 (2022).
Martin-Romero, C., Santos-Alvarez, J., Goberna, R. & Sanchez-Margalet, V. Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell Immunol. 199, 15–24 (2000).
Farooqi, I. S. et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest. 110, 1093–1103 (2002).
Saeed, S. et al. High morbidity and mortality in children with untreated congenital deficiency of leptin or its receptor. Cell Rep. Med. 4, 101187 (2023).
Bracho-Riquelme, R. L., Loera-Castaneda, V., Torres-Valenzuela, A., Loera-Castaneda, G. A. & Sanchez-Ramirez, J. P. Leptin and leptin receptor polymorphisms are associated with poor outcome (death) in patients with non-appendicular secondary peritonitis. Crit. Care 15, R227 (2011).
Bornstein, S. R. et al. Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion. J. Clin. Endocrinol. Metab. 83, 280–283 (1998).
Torpy, D. J., Bornstein, S. R. & Chrousos, G. P. Leptin and interleukin-6 in sepsis. Horm. Metab. Res. 30, 726–729 (1998).
Bracho-Riquelme, R. L., Reyes-Romero, M. A., Pescador, N. & Flores-Garcia, A. I. A leptin serum concentration less than 10 ng/ml is a predictive marker of outcome in patients with moderate to severe secondary peritonitis. Eur. Surg. Res. 41, 238–244 (2008).
Diez, M. L. et al. Serum leptin levels in community acquired pneumonia (CAP) are related to nutritional status and not to acute phase reaction. Cytokine 42, 156–160 (2008).
Arnalich, F. et al. Relationship of plasma leptin to plasma cytokines and human survivalin sepsis and septic shock. J. Infect. Dis. 180, 908–911 (1999).
Catania, A. et al. Plasma concentrations and anti-L-cytokine effects of alpha-melanocyte stimulating hormone in septic patients. Crit. Care Med. 28, 1403–1407 (2000).
Catania, A., Suffredini, A. F. & Lipton, J. M. Endotoxin causes release of alpha-melanocyte-stimulating hormone in normal human subjects. Neuroimmunomodulation 2, 258–262 (1995).
Kemppainen, R. J. & Peterson, M. E. Regulation of alpha-melanocyte-stimulating hormone secretion from the pars intermedia of domestic cats. Am. J. Vet. Res. 60, 245–249 (1999).
Biglari, N. et al. Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting. Nat. Neurosci. 24, 913–929 (2021).
Heisler, L. K. et al. Activation of central melanocortin pathways by fenfluramine. Science 297, 609–611 (2002).
Almond, M. et al. Obesity dysregulates the pulmonary antiviral immune response. Nat. Commun. 14, 6607 (2023).
Ubags, N. D. et al. Hyperleptinemia is associated with impaired pulmonary host defense. JCI Insight 1, e82101 (2016).
Teran-Cabanillas, E., Montalvo-Corral, M., Caire-Juvera, G., Moya-Camarena, S. Y. & Hernandez, J. Decreased interferon-alpha and interferon-beta production in obesity and expression of suppressor of cytokine signaling. Nutrition 29, 207–212 (2013).
Oral, E. A. et al. Leptin-replacement therapy for lipodystrophy. N. Engl. J. Med. 346, 570–578 (2002).
Faggioni, R., Feingold, K. R. & Grunfeld, C. Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J. 15, 2565–2571 (2001).
Bourke, C. D., Berkley, J. A. & Prendergast, A. J. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol. 37, 386–398 (2016).
Black, R. E. et al. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet 371, 243–260 (2008).
Kyriakidis, M., Caetano, L., Anastasiadou, N., Karasu, T. & Lashen, H. Functional hypothalamic amenorrhoea: leptin treatment, dietary intervention and counselling as alternatives to traditional practice — systematic review. Eur. J. Obstet. Gynecol. Reprod. Biol. 198, 131–137 (2016).
Matarese, G. et al. Selective capacity of metreleptin administration to reconstitute CD4+ T-cell number in females with acquired hypoleptinemia. Proc. Natl Acad. Sci. USA 110, E818–E827 (2013).
Matarese, G. et al. Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J. Immunol. 166, 5909–5916 (2001).
De Rosa, V. et al. Leptin neutralization interferes with pathogenic T cell autoreactivity in autoimmune encephalomyelitis. J. Clin. Invest. 116, 447–455 (2006).
Sanna, V. et al. Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses. J. Clin. Invest. 111, 241–250 (2003).
Procaccini, C., Pucino, V., Mantzoros, C. S. & Matarese, G. Leptin in autoimmune diseases. Metabolism 64, 92–104 (2015).
Frisullo, G. et al. The effect of disease activity on leptin, leptin receptor and suppressor of cytokine signalling-3 expression in relapsing-remitting multiple sclerosis. J. Neuroimmunol. 192, 174–183 (2007).
Lock, C. et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. 8, 500–508 (2002).
Tay, M. Z., Poh, C. M., Renia, L., MacAry, P. A. & Ng, L. F. P. The trinity of COVID-19: immunity, inflammation and intervention. Nat. Rev. Immunol. 20, 363–374 (2020).
Group, R. C. et al. Dexamethasone in hospitalized patients with Covid-19. N. Engl. J. Med. 384, 693–704 (2021).
Doi, K. et al. AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality. Kidney Int. 73, 1266–1274 (2008).
Spana, C. et al. Probing the role of melanocortin type 1 receptor agonists in diverse immunological diseases. Front. Pharmacol. 9, 1535 (2018).
US Food and Drug Administration. FDA approves first treatment for weight management for people with certain rare genetic conditions. FDA https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-weight-management-people-certain-rare-genetic-conditions (2020).
Greenfield, J. R. et al. Modulation of blood pressure by central melanocortinergic pathways. N. Engl. J. Med. 360, 44–52 (2009).
Angus, D. C. & van der Poll, T. Severe sepsis and septic shock. N. Engl. J. Med. 369, 840–851 (2013).
Munoz-Rojas, A. R. et al. Leptin signaling maintains autonomic stability during severe influenza infection in mice. J. Clin. Invest. 135, e182550 (2024).
Ouchi, N., Parker, J. L., Lugus, J. J. & Walsh, K. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 11, 85–97 (2011).
