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Inflammatory Cross-Talk Between Short Sleep Duration and Obesity in Development of Insulin Resistance: Narrative Review

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Abstract

Purpose

Obesity is characterized by increased infiltration of macrophages. Cytokines derived from these macrophages significantly induce inflammatory response and desensitize insulin action. Disturbed sleep pattern is also associated with release of the same kind of cytokines that could play a central role in the development of insulin resistance.

Material and Methods

A computer-based search of the literature indexed in PubMed was made using the keywords: glucose metabolism, insulin resistance, adipokines, adiponectin, interleukin-6 (IL-6), leptin, tumor necrosis factor alpha (TNF-α), monocyte chemo-attractant protein-1 (MCP-1), sleep deprivation, and sleep loss. In this review firstly we include the studies that have measured the relationship of cytokines with sleep duration and insulin resistance, and finally, we analyze the relationship of sleep duration with the development of insulin resistance and type 2 diabetes mellitus.

Discussion

IL-6, IL-1β, TNF-α, and MCP-1 are secreted by many cell types including macrophages, adipocytes, etc. They are released in response to many stimuli including sleep loss, tissue injury, and infection. Some evidence has suggested that these cytokines are molecular link between obesity, sleep disturbances, and insulin resistance, because similar types of alterations in plasma levels of these cytokines are found in patients with obesity and disturbed sleep having type 2 diabetes mellitus (DM-2) or insulin resistance.

Conclusion

We conclude that both sleep loss and obesity contribute to the onset of insulin resistance and DM-2 with the help of the same kind of cytokines. The mechanisms involved in the impaired glucose metabolism seem to act via a decreased efficacy of the hypothalamic–pituitary–adrenal (HPA) axis and due to modified release of cytokines—especially IL-1β, IL-6, TNF-α, and MCP-1 from adipocytes following obesity and poor quality of sleep. The aforementioned biomarkers could provide a minimally invasive means for early detection and specific treatment of these disorders.

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References

  1. Kilduff TS, Lein ES, de la Iglesia H, Sakurai T, Fu YH, Shaw P. New developments in sleep research: molecular genetics, gene expression, and systems neurobiology. J Neurosci. 2008;28:11814–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Cirelli C, Tononi G. Gene expression in the brain across the sleep-waking cycle. Brain Res. 2000;885:303–21.

    CAS  PubMed  Google Scholar 

  3. Obal F Jr, Krueger JM. Biochemical regulation of non-rapid-eye-movement sleep. Front Biosci. 2003;8:d520–50.

    CAS  PubMed  Google Scholar 

  4. Krueger JM. The role of cytokines in sleep regulation. Curr Pharm Des. 2008;14:3408–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Spiegel K, Knutson K, Leproult R, Tasali E, Van Cauter E. Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes. J Appl Physiol. 2005;99:2008–19.

    CAS  PubMed  Google Scholar 

  6. Van Cauter E, Blackman JD, Roland D, Spire JP, Refetoff S, Polonsky KS. Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep. J Clin Investig. 1991;88:934–42.

    PubMed  Google Scholar 

  7. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354:1435–9.

    CAS  PubMed  Google Scholar 

  8. Ayas NT, White DP, Manson JE, Stampfer MJ, Speizer FE, Malhotra A, et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med. 2003a;163:205–9.

    PubMed  Google Scholar 

  9. Nilsson PM, Roost M, Engstrom G, Hedblad B, Berglund G. Incidence of diabetes in middle-aged men is related to sleep disturbances. Diabetes Care. 2004;27:2464–9.

    PubMed  Google Scholar 

  10. Mallon L, Broman JE, Hetta J. High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population. Diabetes Care. 2005;28:2762–7.

    PubMed  Google Scholar 

  11. Trenell MI, Marshall NS, Rogers NL. Sleep and metabolic control: waking to a problem? Clin Exp Pharmacol Physiol. 2007;34:1–9.

    CAS  PubMed  Google Scholar 

  12. Reynolds AC, Dorrian J, Liu PY, Van Dongen HP, Wittert GA, Harmer LJ, et al. Impact of five nights of sleep restriction on glucose metabolism, leptin and testosterone in young adult men. PLoS ONE. 2012;7:e41218.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Buxton OM, Pavlova M, Reid EW, Wang W, Simonson DC, Adler GK. Sleep restriction for 1 week reduces insulin sensitivity in healthy men. Diabetes. 2010;59:2126–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Leproult R, Copinschi G, Buxton O, Van CE. Sleep loss results in an elevation of cortisol levels the next evening. Sleep. 1997;20:865–70.

    CAS  PubMed  Google Scholar 

  15. Omisade A, Buxton OM, Rusak B. Impact of acute sleep restriction on cortisol and leptin levels in young women. Physiol Behav. 2010;99:651–6.

    CAS  PubMed  Google Scholar 

  16. Nedeltcheva AV, Kessler L, Imperial J, Penev PD. Exposure to recurrent sleep restriction in the setting of high caloric intake and physical inactivity results in increased insulin resistance and reduced glucose tolerance. J Clin Endocrinol Metab. 2009;94:3242–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Spiegel K, Leproult R, L’hermite-Baleriaux M, Copinschi G, Penev PD, Van CE. Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin. J Clin Endocrinol Metab. 2004;89:5762–71.

    CAS  PubMed  Google Scholar 

  18. Leproult R, Van CE. Effect of 1 week of sleep restriction on testosterone levels in young healthy men. JAMA. 2011;305:2173–4.

    PubMed  PubMed Central  Google Scholar 

  19. Patel SR, Zhu X, Storfer-Isser A, Mehra R, Jenny NS, Tracy R, et al. Sleep duration and biomarkers of inflammation. Sleep. 2009;32:200–4.

    PubMed  PubMed Central  Google Scholar 

  20. Kotani K, Shimohiro H, Sakane N. Mood change tendency and fasting plasma glucose levels in a Japanese female population. Tohoku J Exp Med. 2007;213:369–72.

    PubMed  Google Scholar 

  21. Vgontzas AN, Zoumakis E, Bixler EO, Lin HM, Follett H, Kales A, et al. Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. J Clin Endocrinol Metab. 2004;89:2119–26.

    CAS  PubMed  Google Scholar 

  22. Hayes AL, Xu F, Babineau D, Patel SR. Sleep duration and circulating adipokine levels. Sleep. 2011;34:147–52.

    PubMed  PubMed Central  Google Scholar 

  23. Al-Disi D, Al-Daghri N, Khanam L, Al-Othman A, Al-Saif M, Sabico S, et al. Subjective sleep duration and quality influence diet composition and circulating adipocytokines and ghrelin levels in teen-age girls. Endocr J. 2010;57:915–23.

    CAS  PubMed  Google Scholar 

  24. Kubota T, Li N, Guan Z, Brown RA, Krueger JM. Intrapreoptic microinjection of TNF-alpha enhances non-REM sleep in rats. Brain Res. 2002;932:37–44.

    CAS  PubMed  Google Scholar 

  25. Terao A, Matsumura H, Yoneda H, Saito M. Enhancement of slow-wave sleep by tumor necrosis factor-alpha is mediated by cyclooxygenase-2 in rats. NeuroReport. 1998;9:3791–6.

    CAS  PubMed  Google Scholar 

  26. De Sarro G, Gareri P, Sinopoli VA, David E, Rotiroti D. Comparative, behavioural and electrocortical effects of tumor necrosis factor-alpha and interleukin-1 microinjected into the locus coeruleus of rat. Life Sci. 1997;60:555–64.

    PubMed  Google Scholar 

  27. Manfridi A, Brambilla D, Bianchi S, Mariotti M, Opp MR, Imeri L. Interleukin-1beta enhances non-rapid eye movement sleep when microinjected into the dorsal raphe nucleus and inhibits serotonergic neurons in vitro. Eur J Neurosci. 2003;18:1041–9.

    PubMed  Google Scholar 

  28. Taishi P, Churchill L, Wang M, Kay D, Davis CJ, Guan X, et al. TNF alpha siRNA reduces brain TNF and EEG delta wave activity in rats. Brain Res. 2007;1156:125–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Fang J, Wang Y, Krueger JM. Mice lacking the TNF 55 kDa receptor fail to sleep more after TNF alpha treatment. J Neurosci. 1997;17:5949–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Fang J, Wang Y, Krueger JM. Effects of interleukin-1 beta on sleep are mediated by the type I receptor. Am J Physiol. 1998;274:R655–60.

    CAS  PubMed  Google Scholar 

  31. Kapas L, Bohnet SG, Traynor TR, Majde JA, Szentirmai E, Magrath P, et al. Spontaneous and influenza virus induced sleep are altered in TNF-alpha double-receptor deficient mice. J Appl Physiol. 2008;105:1187–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Darko DF, Miller JC, Gallen C, White J, Koziol J, Brown SJ, et al. Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor alpha, and human immunodeficiency virus infection. Proc Natl Acad Sci USA. 1995;92:12080–4.

    CAS  PubMed  Google Scholar 

  33. Taishi P, Chen Z, Obal F Jr, Hansen MK, Zhang J, Fang J, et al. Sleep-associated changes in interleukin-1beta mRNA in the brain. J Interferon Cytokine Res. 1998;18:793–8.

    CAS  PubMed  Google Scholar 

  34. Krueger JM, Rector DM, Roy S, Van Dongen HP, Belenky G, Panksepp J. Sleep as a fundamental property of neuronal assemblies. Nat Rev Neurosci. 2008;9:910–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Bianco F, Pravettoni E, Colombo A, Schenk U, Möller T, Matteoli M, et al. Astrocyte-derived ATP induces vesicle shedding and IL-1 beta release from microglia. J Immunol. 2005;174:7268–77.

    CAS  PubMed  Google Scholar 

  36. Gabel CA. P2 purinergic receptor modulation of cytokine production. Purinergic Signal. 2007;3:27–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Hide I, Tanaka M, Inoue A, Nakajima K, Kohsaka S, Inoue K, et al. Extracellular ATP triggers tumor necrosis factor alpha release from rat microglia. J Neurochem. 2000;75:965–72.

    CAS  PubMed  Google Scholar 

  38. Suzuki T, Hide I, Ido K, Kohsaka S, Inoue K, Nakata Y. Production and release of neuroprotective tumor necrosis factor by P2X7 receptor-activated microglia. J Neurosci. 2004;24:1–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Hotamisligil GS. Molecular mechanisms of insulin resistance and the role of the adipocyte. Int J Obes Relat Metab Disord. 2000;24:S23–7.

    CAS  PubMed  Google Scholar 

  40. Axelsson J, Rehman J-U, Akerstedt T, Ekman R, Miller GE, et al. Effects of sustained sleep restriction on mitogen-stimulated cytokines, chemokines and T helper 1/T helper 2 balance in humans. PLoS ONE. 2013. https://doi.org/10.1371/journal.pone.0082291.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Vgontzas AN, Papanicolaou DA, Bixler EO, Lotsikas A, Zachman K, Kales A, et al. Circadian interleukin-6 secretion and quantity and depth of sleep. J Clin Endocrinol Metab. 1999;84:2603–7.

    CAS  PubMed  Google Scholar 

  42. Boesen EI, Pollock DM. Effect of chronic IL-6 infusion on acute pressor responses to vasoconstrictors in mice. Am J Physiol Heart Circ Physiol. 2007;293:H1745–9.

    CAS  PubMed  Google Scholar 

  43. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120:1640–5.

    CAS  PubMed  Google Scholar 

  44. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Investig. 2003;112:1821–30.

    CAS  PubMed  Google Scholar 

  45. Odegaard JI, Chawla A. Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis. Science. 2013;339:172–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Investig. 2011;121:2111–7.

    CAS  PubMed  Google Scholar 

  47. Smith U. Impaired (‘diabetic’) insulin signaling and action occur in fat cells long before glucose intolerance is insulin resistance initiated in the adipose tissue? Int J Obes Relat Metab Disord. 2002;26:897–904.

    CAS  PubMed  Google Scholar 

  48. Tack CJ, Stienstra R, Joosten LA, Netea MG. Inflammation links excess fat to insulin resistance: the role of the interleukin-1 family. Immunol Rev. 2012;249:239–52.

    CAS  PubMed  Google Scholar 

  49. Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, et al. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol. 2011;12:408–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Fain JN. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm. 2006;74:443–77.

    CAS  PubMed  Google Scholar 

  51. Koenen TB, Stienstra R, van Tits LJ, Joosten LA, van Velzen JF, Hijmans A, et al. The inflammasome and caspase-1 activation: a new mechanism underlying increased inflammatory activity in human visceral adipose tissue. Endocrinology. 2011;152:3769–78.

    CAS  PubMed  Google Scholar 

  52. Lacasa D, Taleb S, Keophiphath M, Miranville A, Clement K. Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinology. 2007;148:868–77.

    CAS  PubMed  Google Scholar 

  53. Gao D, Madi M, Ding C, Fok M, Steele T, Ford C, et al. Interleukin-1beta mediates macrophage-induced impairment of insulin signaling in human primary adipocytes. Am J Physiol Endocrinol Metab. 2014;307:E289-304.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Gao D, Trayhurn P, Bing C. 1,25-Dihydroxyvitamin D3 inhibits the cytokine-induced secretion of MCP-1 and reduces monocyte recruitment by human preadipocytes. Int J Obes (Lond). 2013;37:357–65.

    CAS  Google Scholar 

  55. Glund S, Deshmukh A, Long YC, Moller T, Koistinen HA, Caidahl K, et al. Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle. Diabetes. 2007;56:1630–7.

    CAS  PubMed  Google Scholar 

  56. Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G, et al. Interleukin-6 increases insulin stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes. 2006;55:2688–97.

    CAS  PubMed  Google Scholar 

  57. Al-Khalili L, Bouzakri K, Glund S, Lonnqvist F, Koistinen HA, Krook A. Signalling specificity of interleukin-6 action on glucose and lipid metabolism in skeletal muscle. Mol Endocrinol. 2006;20:3364–75.

    CAS  PubMed  Google Scholar 

  58. Mullington JM, Haack M, Toth M, Serrador JM, Meier-Ewert HK. Cardiovascular, inflammatory, and metabolic consequences of sleep deprivation. Prog Cardiovasc Dis. 2009;51:294–302.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Soukas A, Cohen P, Socci ND, Friedman JM. Leptin-specific patterns of gene expression in white adipose tissue. Genes Dev. 2000;14:963–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Investig. 2003;112:1796–808.

    CAS  PubMed  Google Scholar 

  61. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Investig. 2005;115:1111–9.

    CAS  PubMed  Google Scholar 

  62. Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Investig. 2003;112:1785–8.

    CAS  PubMed  Google Scholar 

  63. Takahashi K, Mizuarai S, Araki H, Mashiko S, Ishihara A, Kanatani A, et al. Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. J Biol Chem. 2003;278:46654–60.

    CAS  PubMed  Google Scholar 

  64. Christiansen T, Richelsen B, Bruun JM. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int J Obes Relat Metab Disord. 2005;29:146–50.

    CAS  Google Scholar 

  65. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89:2548–56.

    CAS  PubMed  Google Scholar 

  66. Rawat A, Gangwar AK, Tiwari S, Kant S, Garg RK, Singh PK. Sleep quality and insulin resistance in adolescent subjects with different circadian preference: a cross-sectional study. J Fam Med Prim Care. 2019;8:2502–5.

    Google Scholar 

  67. Ayas NT, White DP, Manson JE, Stampfer MJ, Speizer FE, Malhotra A, et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med. 2003b;63:205–9.

    Google Scholar 

  68. Chaput JP, Despres JP, Bouchard C, Astrup A, Tremblay A. Sleep duration as a risk factor for the development of type 2 diabetes or impaired glucose tolerance: analyses of the Quebec Family Study. Sleep Med. 2009;10:919–24.

    PubMed  Google Scholar 

  69. Yaggi HK, Araujo AB, McKinlay JB. Sleep duration as a risk factor for the development of type 2 diabetes. Diabetes Care. 2006;29:657–61.

    PubMed  Google Scholar 

  70. Gottlieb DJ, Punjabi NM, Newman AB, Resnick HE, Redline S, Baldwin CM, et al. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med. 2005;165:863–7.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, All India Institute of Medical Sciences (AIIMS), Gorakhpur, Gorakhpur, India

    Anil Kumar Gangwar

  2. Department of Physiology, Hind Institute of Medical Sciences, Lucknow, India

    Anita Rawat

  3. Department of Physiology, King George’s Medical University, Lucknow, India

    Sunita Tiwari

  4. Department of Pulmonary Medicine, All India Institute of Medical Sciences (AIIMS), Gorakhpur, Gorakhpur, India

    Subodh Kumar

  5. All India Institute of Medical Sciences (AIIMS), Jodhpur, Jodhpur, India

    Praveen Kumar Upadhyay

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  1. Anil Kumar Gangwar
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Gangwar, A.K., Rawat, A., Tiwari, S. et al. Inflammatory Cross-Talk Between Short Sleep Duration and Obesity in Development of Insulin Resistance: Narrative Review. Sleep Vigilance 4, 111–115 (2020). https://doi.org/10.1007/s41782-020-00115-3

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