Adipokines in Critical Illness

  • Katherine Robinson
  • John Prins
  • Bala VenkateshEmail author


Adipose tissue in human can be divided into two main categories, being white adipose tissue and brown adipose tissue. White adipose tissue (WAT) is located in the subcutis (subcutaneous) and in intra-abdominal locations in association with the viscera (visceral). WAT functions as a storage facility, sequestering energy in the form of triglyceride, which is found in the cytoplasmic, unilocular lipid droplet within mature adipocytes. Accumulation or mobilisation of these fat stores occurs in the face of varying energy requirements.


Adipose Tissue Acute Lung Injury Critical Illness Brown Adipose Tissue White Adipose Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Aherne W, Hull D (1966) Brown adipose tissue and heat production in the newborn infant. J Pathol Bacteriol 91(1):223–234CrossRefPubMedGoogle Scholar
  2. 2.
    Cypess AM, Lehman S, Williams G et al (2009) Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360(15):1509–1517CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Smorlesi A, Frontini A, Giordano A, Cinti S (2012) The adipose organ: white-brown adipocyte plasticity and metabolic inflammation. Obes Rev 13(Suppl 2):83–96CrossRefPubMedGoogle Scholar
  4. 4.
    Kloting N, Bluher M (2014) Adipocyte dysfunction, inflammation and metabolic syndrome. Rev Endocr Metab Disord 15(4):277–287CrossRefPubMedGoogle Scholar
  5. 5.
    Exley MA, Hand L, O'Shea D, Lynch L (2014) Interplay between the immune system and adipose tissue in obesity. J Endocrinol 223(2):R41–R48CrossRefPubMedGoogle Scholar
  6. 6.
    Park HS, Park JY, Yu R (2005) Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6. Diabetes Res Clin Pract 69(1):29–35CrossRefPubMedGoogle Scholar
  7. 7.
    Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11(2):85–97CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wellhoener P, Vietheer A, Sayk F, Schaaf B, Lehnert H, Dodt C (2011) Metabolic alterations in adipose tissue during the early phase of experimental endotoxemia in humans. Horm Metab Res 43(11):754–759CrossRefPubMedGoogle Scholar
  9. 9.
    Robinson K, Kruger P, Prins J, Venkatesh B (2011) The metabolic syndrome in critically ill patients. Best Pract Res Clin Endocrinol Metab 25(5):835–845CrossRefPubMedGoogle Scholar
  10. 10.
    Otero M, Lago R, Lago F et al (2005) Leptin, from fat to inflammation: old questions and new insights. FEBS Lett 579(2):295–301CrossRefPubMedGoogle Scholar
  11. 11.
    Gheorghita V, Barbu AE, Gheorghiu ML, Caruntu FA (2015) Endocrine dysfunction in sepsis: a beneficial or deleterious host response? Germs 5(1):17–25CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Chen KK (2006) Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nat Med 12(4):425–432CrossRefPubMedGoogle Scholar
  13. 13.
    Paz-Filho G, Mastronardi C, Franco CB, Wang KB, Wong ML, Licinio J (2012) Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications. Arq Bras Endocrinol Metabol 56(9):597–607CrossRefPubMedGoogle Scholar
  14. 14.
    Hekerman P, Zeidler J, Korfmacher S et al (2007) Leptin induces inflammation-related genes in RINm5F insulinoma cells. BMC Mol Biol 8:41CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Siegl D, Annecke T, Johnson BL 3rd et al (2014) Obesity-induced hyperleptinemia improves survival and immune response in a murine model of sepsis. Anesthesiology 121(1):98–114CrossRefPubMedGoogle Scholar
  16. 16.
    Landgraf MA, Silva RC, Correa-Costa M et al (2014) Leptin downregulates LPS-induced lung injury: role of corticosterone and insulin. Cell Physiol Biochem 33(3):835–846CrossRefPubMedGoogle Scholar
  17. 17.
    Chen M, Wang B, Xu Y et al (2014) Diagnostic value of serum leptin and a promising novel diagnostic model for sepsis. Exp Ther Med 7(4):881–886PubMedPubMedCentralGoogle Scholar
  18. 18.
    Yousef AA, Amr YM, Suliman GA (2010) The diagnostic value of serum leptin monitoring and its correlation with tumor necrosis factor-alpha in critically ill patients: a prospective observational study. Crit Care 14(2):R33CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Koch A, Weiskirchen R, Zimmermann HW, Sanson E, Trautwein C, Tacke F. Relevance of serum leptin and leptin-receptor concentrations in critically ill patients. Mediators Inflamm. 2010;2010. doi: 10.1155/2010/473540
  20. 20.
    Garten A, Petzold S, Schuster S, Korner A, Kratzsch J, Kiess W (2011) Nampt and its potential role in inflammation and type 2 diabetes. Handb Exp Pharmacol 203:147–164CrossRefPubMedGoogle Scholar
  21. 21.
    Garten A, Schuster S, Penke M, Gorski T, de Giorgis T, Kiess W (2015) Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol 11(9):535–546PubMedGoogle Scholar
  22. 22.
    Fukuhara A, Matsuda M, Nishizawa M et al (2005) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307(5708):426–430CrossRefPubMedGoogle Scholar
  23. 23.
    Jia SH, Li Y, Parodo J et al (2004) Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest 113(9):1318–1327CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Hong SB, Huang Y, Moreno-Vinasco L et al (2008) Essential role of pre-B-cell colony enhancing factor in ventilator-induced lung injury. Am J Respir Crit Care Med 178(6):605–617CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Camp SM, Ceco E, Evenoski CL et al (2015) Unique toll-like receptor 4 activation by NAMPT/PBEF induces NFkappaB signaling and inflammatory lung injury. Sci Rep 5:13135CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ye SQ, Simon BA, Maloney JP et al (2005) Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury. Am J Respir Crit Care Med 171(4):361–370CrossRefPubMedGoogle Scholar
  27. 27.
    Lee KA, Gong MN (2011) Pre-B-cell colony-enhancing factor and its clinical correlates with acute lung injury and sepsis. Chest 140(2):382–390CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Lee K, Huh JW, Lim CM, Koh Y, Hong SB (2013) Clinical role of serum pre-B cell colony-enhancing factor in ventilated patients with sepsis and acute respiratory distress syndrome. Scand J Infect Dis 45(10):760–765CrossRefPubMedGoogle Scholar
  29. 29.
    Hu W, Liu CW, Su J, Lu J, Zhu Y, Liu BW (2013) Elevated plasma visfatin concentrations in patients with community-acquired pneumonia. Peptides 43:8–12CrossRefPubMedGoogle Scholar
  30. 30.
    Ferreira AC, Da Mesquita S, Sousa JC et al (2015) From the periphery to the brain: Lipocalin-2, a friend or foe? Prog Neurobiol 131:120–136CrossRefPubMedGoogle Scholar
  31. 31.
    Chakraborty S, Kaur S, Guha S, Batra SK (2012) The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer. Biochim Biophys Acta 1826(1):129–169PubMedPubMedCentralGoogle Scholar
  32. 32.
    Martensson J, Bell M, Oldner A, Xu S, Venge P, Martling CR (2010) Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury. Intensive Care Med 36(8):1333–1340CrossRefPubMedGoogle Scholar
  33. 33.
    Zhang Y, Foncea R, Deis JA, Guo H, Bernlohr DA, Chen X (2014) Lipocalin 2 expression and secretion is highly regulated by metabolic stress, cytokines, and nutrients in adipocytes. PLoS One 9(5):e96997CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Zhang J, Wu Y, Zhang Y, Leroith D, Bernlohr DA, Chen X (2008) The role of lipocalin 2 in the regulation of inflammation in adipocytes and macrophages. Mol Endocrinol 22(6):1416–1426CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Axelsson L, Bergenfeldt M, Ohlsson K (1995) Studies of the release and turnover of a human neutrophil lipocalin. Scand J Clin Lab Invest 55(7):577–588CrossRefPubMedGoogle Scholar
  36. 36.
    Chakraborty S, Kaur S, Muddana V et al (2010) Elevated serum neutrophil gelatinase-associated lipocalin is an early predictor of severity and outcome in acute pancreatitis. Am J Gastroenterol 105(9):2050–2059CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Kangelaris KN, Prakash A, Liu KD et al (2015) Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS. Am J Physiol Lung Cell Mol Physiol 308(11):L1102–L1113CrossRefPubMedGoogle Scholar
  38. 38.
    Bell M, Larsson A, Venge P, Bellomo R, Martensson J (2015) Assessment of cell-cycle arrest biomarkers to predict early and delayed acute kidney injury. Dis Markers 2015:158658CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Martensson J, Bell M, Xu S et al (2013) Association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with sepsis and acute kidney dysfunction. Biomarkers Biochem Indicators Expo Response Susceptibility Chem 18(4):349–356Google Scholar
  40. 40.
    Wang B, Chen G, Zhang J, Xue J, Cao Y, Wu Y (2015) Increased NGAL is associated with mortality and multiple organ dysfunction syndrome in severe sepsis and septic shock. Shock 44:234–238CrossRefPubMedGoogle Scholar
  41. 41.
    Robinson K, Prins J, Venkatesh B (2011) Clinical review: adiponectin biology and its role in inflammation and critical illness. Crit Care 15(2):221CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Comuzzie AG, Funahashi T, Sonnenberg G et al (2001) The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab 86(9):4321–4325CrossRefPubMedGoogle Scholar
  43. 43.
    Seino Y, Hirose H, Saito I, Itoh H (2007) High molecular weight multimer form of adiponectin as a useful marker to evaluate insulin resistance and metabolic syndrome in Japanese men. Metabolism 56(11):1493–1499CrossRefPubMedGoogle Scholar
  44. 44.
    Scheer FA, Chan JL, Fargnoli J et al (2010) Day/night variations of high-molecular-weight adiponectin and lipocalin-2 in healthy men studied under fed and fasted conditions. Diabetologia 53(11):2401–2405CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Robinson K, Jones M, Ordonez J et al (2013) Random measurements of adiponectin and IL-6 may not be indicative of the 24-h profile in critically ill patients. Clin Endocrinol (Oxf) 79(6):892–898CrossRefGoogle Scholar
  46. 46.
    Gavrila A, Peng C-K, Chan JL, Mietus JE, Goldberger AL, Mantzoros CS (2003) Diurnal and ultradian dynamics of serum adiponectin in healthy men: comparison with leptin, circulating soluble leptin receptor, and cortisol patterns. J Clin Endocrinol Metab 88(6):2838–2843CrossRefPubMedGoogle Scholar
  47. 47.
    Yamauchi T, Nio Y, Maki T et al (2007) Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 13(3):332–339CrossRefPubMedGoogle Scholar
  48. 48.
    Yamauchi T, Kamon J, Ito Y et al (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423(6941):762–769CrossRefPubMedGoogle Scholar
  49. 49.
    Kharroubi I, Rasschaert J, Eizirik DL, Cnop M (2003) Expression of adiponectin receptors in pancreatic beta cells. Biochem Biophys Res Commun 312(4):1118–1122CrossRefPubMedGoogle Scholar
  50. 50.
    Chinetti G, Zawadski C, Fruchart JC, Staels B (2004) Expression of adiponectin receptors in human macrophages and regulation by agonists of the nuclear receptors PPARalpha, PPARgamma, and LXR. Biochem Biophys Res Commun 314(1):151–158CrossRefPubMedGoogle Scholar
  51. 51.
    Ding G, Qin Q, He N et al (2007) Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor gamma. J Mol Cell Cardiol 43(1):73–84CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Nannipieri M, Bonotti A, Anselmino M et al (2007) Pattern of expression of adiponectin receptors in human adipose tissue depots and its relation to the metabolic state. Int J Obes 31(12):1843–1848CrossRefGoogle Scholar
  53. 53.
    Thundyil J, Pavlovski D, Sobey CG, Arumugam TV (2012) Adiponectin receptor signalling in the brain. Br J Pharmacol 165(2):313–327CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Psilopanagioti A, Papadaki H, Kranioti EF, Alexandrides TK, Varakis JN (2009) Expression of adiponectin and adiponectin receptors in human pituitary gland and brain. Neuroendocrinology 89(1):38–47CrossRefPubMedGoogle Scholar
  55. 55.
    Parker-Duffen JL, Walsh K (2014) Cardiometabolic effects of adiponectin. Best Pract Res Clin Endocrinol Metab 28(1):81–91CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Lira FS, Rosa JC, Pimentel GD et al (2012) Both adiponectin and interleukin-10 inhibit LPS-induced activation of the NF-kappaB pathway in 3T3-L1 adipocytes. Cytokine 57(1):98–106CrossRefPubMedGoogle Scholar
  57. 57.
    Park PH, McMullen MR, Huang H, Thakur V, Nagy LE (2007) Short-term treatment of RAW264.7 macrophages with adiponectin increases tumor necrosis factor-alpha (TNF-alpha) expression via ERK1/2 activation and Egr-1 expression: role of TNF-alpha in adiponectin-stimulated interleukin-10 production. J Biol Chem 282(30):21695–21703CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Pang TT, Narendran P (2008) The distribution of adiponectin receptors on human peripheral blood mononuclear cells. Ann N Y Acad Sci 1150:143–145CrossRefPubMedGoogle Scholar
  59. 59.
    Lang K, Ratke J (2009) Leptin and Adiponectin: new players in the field of tumor cell and leukocyte migration. Cell Commun Signal 7:27CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Siso S, Jeffrey M, Gonzalez L (2010) Sensory circumventricular organs in health and disease. Acta Neuropathol 120(6):689–705CrossRefPubMedGoogle Scholar
  61. 61.
    Fry M, Smith PM, Hoyda TD et al (2006) Area postrema neurons are modulated by the adipocyte hormone adiponectin. J Neurosci 26(38):9695–9702CrossRefPubMedGoogle Scholar
  62. 62.
    Alim I, Fry WM, Walsh MH, Ferguson AV (2010) Actions of adiponectin on the excitability of subfornical organ neurons are altered by food deprivation. Brain Res 1330:72–82CrossRefPubMedGoogle Scholar
  63. 63.
    Iwasa T, Matsuzaki T, Matsui S et al (2014) The effects of LPS-induced endotoxemia on the expression of adiponectin and its receptors in female rats. Endocr J 61(9):891–900CrossRefPubMedGoogle Scholar
  64. 64.
    Hoyda TD, Smith PM, Ferguson AV (2009) Adiponectin acts in the nucleus of the solitary tract to decrease blood pressure by modulating the excitability of neuropeptide Y neurons. Brain Res 1256:76–84CrossRefPubMedGoogle Scholar
  65. 65.
    Tsuchihashi H, Yamamoto H, Maeda K et al (2006) Circulating concentrations of adiponectin, an endogenous lipopolysaccharide neutralizing protein, decrease in rats with polymicrobial sepsis. J Surg Res 134(2):348–353CrossRefPubMedGoogle Scholar
  66. 66.
    Jernas M, Olsson B, Sjoholm K et al (2009) Changes in adipose tissue gene expression and plasma levels of adipokines and acute-phase proteins in patients with critical illness. Metabolism 58(1):102–108CrossRefPubMedGoogle Scholar
  67. 67.
    Venkatesh B, Hickman I, Nisbet J, Cohen J, Prins J (2009) Changes in serum adiponectin concentrations in critical illness: a preliminary investigation. Crit Care 13(4):R105CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Langouche L, Vander Perre S, Frystyk J, Flyvbjerg A, Hansen TK, Van den Berghe G (2009) Adiponectin, retinol-binding protein 4, and leptin in protracted critical illness of pulmonary origin. Crit Care 13(4):R112CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Takeuchi S, Wada K, Otani N, Osada H, Nagatani K, Mori K (2014) Temporal profile of plasma adiponectin level and delayed cerebral ischemia in patients with subarachnoid hemorrhage. J Clin Neurosci 21(6):1007–1010CrossRefPubMedGoogle Scholar
  70. 70.
    Keller P, Moller K, Krabbe KS, Pedersen BK (2003) Circulating adiponectin levels during human endotoxaemia. Clin Exp Immunol 134(1):107–110CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Anderson PD, Mehta NN, Wolfe ML et al (2007) Innate immunity modulates adipokines in humans. J Clin Endocrinol Metab 92(6):2272–2279CrossRefPubMedGoogle Scholar
  72. 72.
    Kaplan JM, Denenberg A, Monaco M, Nowell M, Wong H, Zingarelli B (2010) Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock. Intensive Care Med 36(1):123–130CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Walkey AJ, Rice TW, Konter J et al (2010) Plasma adiponectin and mortality in critically ill subjects with acute respiratory failure. Crit Care Med 38(12):2329–2334CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Codoner-Franch P, Alonso-Iglesias E (2015) Resistin: insulin resistance to malignancy. Clin Chim Acta 438:46–54CrossRefPubMedGoogle Scholar
  75. 75.
    Koch A, Gressner OA, Sanson E, Tacke F, Trautwein C (2009) Serum resistin levels in critically ill patients are associated with inflammation, organ dysfunction and metabolism and may predict survival of non-septic patients. Crit Care 13(3):R95CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Sunden-Cullberg J, Nystrom T, Lee ML et al (2007) Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock. Crit Care Med 35(6):1536–1542CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Katherine Robinson
    • 1
  • John Prins
    • 1
  • Bala Venkatesh
    • 1
    Email author
  1. 1.Intensive Care Unit, Wesley HospitalUniversity of QueenslandSt LuciaAustralia

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