Skip to main content

Advertisement

SpringerLink
Log in

Contributors to Metabolic Disease Risk Following Spinal Cord Injury

  • Spinal Cord Injury Rehabilitation (Christina Sadowsky, Section Editor)
  • Published:
Current Physical Medicine and Rehabilitation Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Spinal cord injury (SCI)-induced changes in neurological function have significant impact on the metabolism and subsequent metabolic-related disease risk in injured individuals. Although alterations in body composition, particularly excess adiposity and its anatomical distribution in the visceral depot or ectopic location in nonadipose organs, are known to significantly contribute to metabolic disease risk, changes in fat mass and fat-free mass do not fully account for this elevated disease risk in subjects with SCI.

Recent Findings

There are other negative adaptations in body composition including reductions in skeletal muscle mass and alterations in muscle fiber type, in addition to significant reduction in physical activity, which contribute to a decline in metabolic rate and increased metabolic disease risk following SCI. Recent studies in adult humans suggest that cold- and diet-induced thermogenesis through brown adipose tissue (BAT) metabolism may be important for energy balance and substrate metabolism, and particularly sensitive to sympathetic nervous signaling.

Summary

Considering the physiologic and metabolic phenotypes observed with SCI, particularly across varying anatomic levels, understanding BAT function and impairment with SCI may help improve clinical practice for subjects with SCI while bringing clarity to a broader understanding of the metabolic significance of BAT in adult humans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Recently published papers of particular interest have been highlighted as: ∙ Of importance

  1. Spinal cord injury (SCI) facts and figures at a glance. J Spinal Cord Med. 2016;39:243–4. https://www.nscisc.uab.edu/Public/Facts%202015%20Aug.pdf.

  2. Jensen MP, Molton IR, Groah SL, Campbell ML, Charlifue S, Chiodo A, Forchheimer M, Krause JS, Tate D. Secondary health conditions in individuals aging with SCI: terminology, concepts and analytic approaches. Spinal Cord. 2012;50:373–8.

    CAS  PubMed  Google Scholar 

  3. Duckworth WC, Solomon SS, Jallepalli P, Heckemeyer C, Finnern J, Powers A. Glucose intolerance due to insulin resistance in patients with spinal cord injuries. Diabetes. 1980;29:906–10.

    CAS  PubMed  Google Scholar 

  4. Bauman WA, Spungen AM. Disorders of carbohydrate and lipid metabolism in veterans with paraplegia or quadriplegia: a model of premature aging. Metabolism. 1994;43:749–56.

    CAS  PubMed  Google Scholar 

  5. Bauman WA, Adkins RH, Spungen AM, Waters RL. The effect of residual neurological deficit on oral glucose tolerance in persons with chronic spinal cord injury. Spinal Cord. 1999;37:765–71.

    CAS  PubMed  Google Scholar 

  6. • Bauman WA, Spungen AM. Carbohydrate and lipid metabolism in chronic spinal cord injury. J Spinal Cord Med. 2001;24:266–77. Demonstrates that when compared with the able-bodied population, people with spinal cord injury are more likely to have oral carbohydrate and lipid disorders which are associated with increased prevalences of diabetes mellitus and cardiovascular disease.

  7. Bauman WA, Spungen AM. Coronary heart disease in individuals with spinal cord injury: assessment of risk factors. Spinal Cord. 2008;46:466–76.

    CAS  PubMed  Google Scholar 

  8. Kressler J, Cowan RE, Bigford GE, Nash MS. Reducing cardiometabolic disease in spinal cord injury. Phys Med Rehabil Clin N Am. 2014;25:573–604, viii.

    PubMed  Google Scholar 

  9. Banerjea R, Sambamoorthi U, Weaver F, Maney M, Pogach LM, Findley T. Risk of stroke, heart attack, and diabetes complications among veterans with spinal cord injury. Arch Phys Med Rehabil. 2008;89:1448–53.

    PubMed  Google Scholar 

  10. Bluvshtein V, Korczyn AD, Pinhas I, Vered Y, Gelernter I, Catz A. Insulin resistance in tetraplegia but not in mid-thoracic paraplegia: Is the mid-thoracic spinal cord involved in glucose regulation? Spinal Cord. 2011;49:648–52.

    CAS  PubMed  Google Scholar 

  11. Karlsson AK. Insulin resistance and sympathetic function in high spinal cord injury. Spinal Cord. 1999;37:494–500.

    CAS  PubMed  Google Scholar 

  12. Buchholz AC, Pencharz PB. Energy expenditure in chronic spinal cord injury. Curr Opin Clin Nutr Metab Care. 2004;7:635–9.

    PubMed  Google Scholar 

  13. Raymond J, Harmer AR, Temesi J, van Kemenade C. Glucose tolerance and physical activity level in people with spinal cord injury. Spinal Cord. 2010;48:591–6.

    CAS  PubMed  Google Scholar 

  14. Schmid A, Halle M, Stutzle C, Konig D, Baumstark MW, Storch MJ, Schmidt-Trucksass A, Lehmann M, Berg A, Keul J. Lipoproteins and free plasma catecholamines in spinal cord injured men with different injury levels. Clin Physiol. 2000;20:304–10.

    CAS  PubMed  Google Scholar 

  15. Monroe MB, Tataranni PA, Pratley R, Manore MM, Skinner JS, Ravussin E. Lower daily energy expenditure as measured by a respiratory chamber in subjects with spinal cord injury compared with control subjects. Am J Clin Nutr. 1998;68:1223–7.

    CAS  PubMed  Google Scholar 

  16. Storch MJ, Konig D, Bultermann D, Blum A, Vogt S, Baumstark M, Berg A, Schmid A. Lipid profile in spinal cord-injured women with different injury levels. Prev Med. 2005;40:321–5.

    CAS  PubMed  Google Scholar 

  17. Myers J, Lee M, Kiratli J. Cardiovascular disease in spinal cord injury: an overview of prevalence, risk, evaluation, and management. Am J Phys Med Rehabil. 2007;86:142–52.

    PubMed  Google Scholar 

  18. Schmid A, Huonker M, Stahl F, Barturen JM, Konig D, Heim M, Lehmann M, Keul J. Free plasma catecholamines in spinal cord injured persons with different injury levels at rest and during exercise. J Auton Nerv Syst. 1998;68:96–100.

    CAS  PubMed  Google Scholar 

  19. Menard MR, Hahn G. Acute and chronic hypothermia in a man with spinal cord injury: environmental and pharmacologic causes. Arch Phys Med Rehabil. 1991;72:421–4.

    CAS  PubMed  Google Scholar 

  20. Colachis SC III. Hypothermia associated with autonomic dysreflexia after traumatic spinal cord injury. Am J Phys Med Rehabil. 2002;81:232–5.

    PubMed  Google Scholar 

  21. Khan S, Plummer M, Martinez-Arizala A, Banovac K. Hypothermia in patients with chronic spinal cord injury. J Spinal Cord Med. 2007;30:27–30.

    PubMed  PubMed Central  Google Scholar 

  22. Landsberg L, Saville ME, Young JB. Sympathoadrenal system and regulation of thermogenesis. Am J Physiol. 1984;247:E181–9.

    CAS  PubMed  Google Scholar 

  23. Duale H, Hou S, Derbenev AV, Smith BN, Rabchevsky AG. Spinal cord injury reduces the efficacy of pseudorabies virus labeling of sympathetic preganglionic neurons. J Neuropathol Exp Neurol. 2009;68:168–78.

    PubMed  Google Scholar 

  24. Lucin KM, Sanders VM, Popovich PG. Stress hormones collaborate to induce lymphocyte apoptosis after high level spinal cord injury. J Neurochem. 2009;110:1409–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Lucin KM, Sanders VM, Jones TB, Malarkey WB, Popovich PG. Impaired antibody synthesis after spinal cord injury is level dependent and is due to sympathetic nervous system dysregulation. Exp Neurol. 2007;207:75–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Attia M, Engel P. Thermoregulatory set point in patients with spinal cord injuries (spinal man). Paraplegia. 1983;21:233–48.

    CAS  PubMed  Google Scholar 

  27. Chu A, Burnham RS. Reliability and validity of tympanic temperature measurement in persons with high spinal cord injuries. Paraplegia. 1995;33:476–9.

    CAS  PubMed  Google Scholar 

  28. Garstang SV, Miller-Smith SA. Autonomic nervous system dysfunction after spinal cord injury. Phys Med Rehabil Clin N Am. 2007;18:275-96.

    PubMed  Google Scholar 

  29. Hagen EM, Rekand T, Gronning M, Faerestrand S. Cardiovascular complications of spinal cord injury. Tidsskr Nor Laegeforen. 2012;132:1115–20.

    PubMed  Google Scholar 

  30. Koeppen AH. Subnormal body temperatures in spinal cord injury. Neurology. 1985;35:1259–60.

    CAS  PubMed  Google Scholar 

  31. Taylor RG. Spinal cord injury: its many complications. Am Fam Physician. 1973;8:138–46.

    CAS  PubMed  Google Scholar 

  32. Thijssen DH, Eijsvogels TM, Hesse M, Ballak DB, Atkinson G, Hopman MT. The effects of thoracic and cervical spinal cord lesions on the circadian rhythm of core body temperature. Chronobiol Int. 2011;28:146–54.

    PubMed  Google Scholar 

  33. Weaver LC, Fleming JC, Mathias CJ, Krassioukov AV. Disordered cardiovascular control after spinal cord injury. Handb Clin Neurol. 2012;109:213–33.

    PubMed  Google Scholar 

  34. Castro MJ, Apple DF Jr., Staron RS, Campos GE, Dudley GA. Influence of complete spinal cord injury on skeletal muscle within 6 mo of injury. J Appl Physiol. (1985). 1999;86:350–8.

    CAS  Google Scholar 

  35. Kocina P. Body composition of spinal cord injured adults. Sports Med. 1997;23:48–60.

    CAS  PubMed  Google Scholar 

  36. Spungen AM, Bauman WA, Wang J, Pierson RN Jr.. Measurement of body fat in individuals with tetraplegia: a comparison of eight clinical methods. Paraplegia. 1995;33:402–8.

    CAS  PubMed  Google Scholar 

  37. Chen Y, Cao Y, Allen V, Richards JS. Weight matters: physical and psychosocial well being of persons with spinal cord injury in relation to body mass index. Arch Phys Med Rehabil. 2011;92:391–8.

    PubMed  Google Scholar 

  38. Romero-Corral A, Somers VK, Sierra-Johnson J, Thomas RJ, Collazo-Clavell ML, Korinek J, Allison TG, Batsis JA, Sert-Kuniyoshi FH, Lopez-Jimenez F. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes (Lond.). 2008;32:959–66.

    CAS  Google Scholar 

  39. Gater Jr. DR. Obesity after spinal cord injury. Phys Med Rehabil Clin N Am. 2007;18:333–51, vii.

  40. Gupta N, White KT, Sandford PR. Body mass index in spinal cord injury—a retrospective study. Spinal Cord. 2006;44:92–4.

    CAS  PubMed  Google Scholar 

  41. Yarar-Fisher C, Chen Y, Jackson AB, Hunter GR. Body mass index underestimates adiposity in women with spinal cord injury. Obesity (Silver Spring). 2013;21:1223–5.

    Google Scholar 

  42. Buchholz AC, Bugaresti JM. A review of body mass index and waist circumference as markers of obesity and coronary heart disease risk in persons with chronic spinal cord injury. Spinal Cord. 2005;43:513–8.

    CAS  PubMed  Google Scholar 

  43. Laughton GE, Buchholz AC, Martin Ginis KA, Goy RE. Lowering body mass index cutoffs better identifies obese persons with spinal cord injury. Spinal Cord. 2009;47:757–62.

    CAS  PubMed  Google Scholar 

  44. Edwards LA, Bugaresti JM, Buchholz AC. Visceral adipose tissue and the ratio of visceral to subcutaneous adipose tissue are greater in adults with than in those without spinal cord injury, despite matching waist circumferences. Am J Clin Nutr. 2008;87:600–7.

    CAS  PubMed  Google Scholar 

  45. Gorgey AS, Wells KM, Austin TL. Adiposity and spinal cord injury. World J. Orthop. 2015;6:567–76.

    PubMed  PubMed Central  Google Scholar 

  46. Hu HH, Chen J, Shen W. Segmentation and quantification of adipose tissue by magnetic resonance imaging. MAGMA 2016;29:259–76.

    CAS  PubMed  Google Scholar 

  47. Machann J, Horstmann A, Born M, Hesse S, Hirsch FW. Diagnostic imaging in obesity. Best Pract Res Clin Endocrinol Metab. 2013;27:261–77.

    PubMed  Google Scholar 

  48. Castro MJ, Apple DF Jr., Hillegass EA, Dudley GA. Influence of complete spinal cord injury on skeletal muscle cross-sectional area within the first 6 months of injury. Eur J Appl Physiol Occup Physiol. 1999;80:373–8.

    CAS  PubMed  Google Scholar 

  49. McCully KK, Mulcahy TK, Ryan TE, Zhao Q. Skeletal muscle metabolism in individuals with spinal cord injury. J Appl Physiol. (1985). 2011;111:143–8.

    Google Scholar 

  50. Bickel CS, Yarar-Fisher C, Mahoney ET, McCully KK. Neuromuscular electrical stimulation-induced resistance training after SCI: a review of the Dudley protocol. Top Spinal Cord Inj Rehabil. 2015;21:294–302.

    PubMed  PubMed Central  Google Scholar 

  51. Breda E, Cavaghan MK, Toffolo G, Polonsky KS, Cobelli C. Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity. Diabetes. 2001;50:150–8.

    CAS  PubMed  Google Scholar 

  52. Bickel CS, Slade JM, VanHiel LR, Warren GL, Dudley GA. Variable-frequency-train stimulation of skeletal muscle after spinal cord injury. J Rehabil Res Dev. 2004;41:33–40.

    PubMed  Google Scholar 

  53. Zierath JR, Krook A, Wallberg-Henriksson H. Insulin action in skeletal muscle from patients with NIDDM. Mol Cell Biochem. 1998;182:153–60.

    CAS  PubMed  Google Scholar 

  54. Albers PH, Pedersen AJ, Birk JB, Kristensen DE, Vind BF, Baba O, Nohr J, Hojlund K, Wojtaszewski JF. Human muscle fiber type-specific insulin signaling: impact of obesity and type 2 diabetes. Diabetes. 2015;64:485–97.

    CAS  PubMed  Google Scholar 

  55. Yarar-Fisher C, Bickel CS, Windham ST, McLain AB, Bamman MM. Skeletal muscle signaling associated with impaired glucose tolerance in spinal cord-injured men and the effects of contractile activity. J Appl Physiol. (1985). 2013;115:756–64.

    CAS  Google Scholar 

  56. Martinez JA, Fruhbeck G. Regulation of energy balance and adiposity: a model with new approaches. Rev Esp Fisiol. 1996;52:255–8.

    CAS  PubMed  Google Scholar 

  57. Krassioukov AV, Karlsson AK, Wecht JM, Wuermser LA, Mathias CJ, Marino RJ. Assessment of autonomic dysfunction following spinal cord injury: rationale for additions to International Standards for Neurological Assessment. J Rehabil Res Dev. 2007;44:103–12.

    PubMed  Google Scholar 

  58. Alexander MS, Biering-Sorensen F, Bodner D, Brackett NL, Cardenas D, Charlifue S, Creasey G, Dietz V, Ditunno J, Donovan W, Elliott SL, Estores I, Graves DE, Green B, Gousse A, Jackson AB, Kennelly M, Karlsson AK, Krassioukov A, Krogh K, Linsenmeyer T, Marino R, Mathias CJ, Perkash I, Sheel AW, Schilero G, Schurch B, Sonksen J, Stiens S, Wecht J, Wuermser LA, Wyndaele JJ. International standards to document remaining autonomic function after spinal cord injury. Spinal Cord. 2009;47:36–43.

    CAS  PubMed  Google Scholar 

  59. Wecht JM, La Fountaine MF, Handrakis JP, West CR, Phillips A, Ditor DS, Sharif H, Bauman WA, Krassioukov AV. Autonomic nervous system dysfunction following spinal cord injury: cardiovascular, cerebrovascular, and thermoregulatory effects. Curr Phys Med Rehabil Rep. 2015;3:197–205.

    Google Scholar 

  60. Cabanac M. Temperature regulation. Annu Rev Physiol. 1975;37:415–39.

    CAS  PubMed  Google Scholar 

  61. Yilmaz B, Yasar E, Goktepe S, Alaca R, Yazicioglu K, Dal U, Mohur H. Basal metabolic rate and autonomic nervous system dysfunction in men with spinal cord injury. Obesity (Silver Spring). 2007;15:2683–7.

    Google Scholar 

  62. Jequier E, Schutz Y. Long-term measurements of energy expenditure in humans using a respiration chamber. Am J Clin Nutr. 1983;38:989–98.

    CAS  PubMed  Google Scholar 

  63. Raven PB, Wilkerson JE, Horvath SM, Bolduan NW. Thermal, metabolic, and cardiovascular responses to various degrees of cold stress. Can J Physiol Pharmacol. 1975;53:293–8.

    CAS  PubMed  Google Scholar 

  64. Dauncey MJ. Influence of mild cold on 24 h energy expenditure, resting metabolism and diet-induced thermogenesis. Br J Nutr. 1981;45:257–67.

    CAS  PubMed  Google Scholar 

  65. van Marken Lichtenbelt WD, Daanen HA. Cold-induced metabolism. Curr Opin Clin Nutr Metab Care. 2003;6:469–75.

    PubMed  Google Scholar 

  66. van Ooijen AM, van Marken Lichtenbelt WD, van Steenhoven AA, Westerterp KR. Seasonal changes in metabolic and temperature responses to cold air in humans. Physiol Behav. 2004;82:545–53.

    PubMed  Google Scholar 

  67. Wijers SL, Saris WH, van Marken Lichtenbelt WD. Individual thermogenic responses to mild cold and overfeeding are closely related. J Clin Endocrinol Metab. 2007;92:4299–305.

    CAS  PubMed  Google Scholar 

  68. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84:277–359.

    CAS  PubMed  Google Scholar 

  69. Steiner G, Loveland M, Schonbaum E. Effect of denervation on brown adipose tissue metabolism. Am J Physiol. 1970;218:566–70.

    CAS  PubMed  Google Scholar 

  70. Mollinger LA, Spurr GB, el Ghatit AZ, Barboriak JJ, Rooney CB, Davidoff DD, Bongard RD. Daily energy expenditure and basal metabolic rates of patients with spinal cord injury. Arch Phys Med Rehabil. 1985;66:420–6.

    CAS  PubMed  Google Scholar 

  71. Alexander LR, Spungen AM, Liu MH, Losada M, Bauman WA. Resting metabolic rate in subjects with paraplegia: the effect of pressure sores. Arch Phys Med Rehabil. 1995;76:819–22.

    CAS  PubMed  Google Scholar 

  72. Jeon JY, Steadward RD, Wheeler GD, Bell G, McCargar L, Harber V. Intact sympathetic nervous system is required for leptin effects on resting metabolic rate in people with spinal cord injury. J Clin Endocrinol Metab. 2003;88:402–7.

    CAS  PubMed  Google Scholar 

  73. Bauman WA, Spungen AM, Wang J, Pierson RN Jr. The relationship between energy expenditure and lean tissue in monozygotic twins discordant for spinal cord injury. J Rehabil Res Dev. 2004;41:1–8.

    PubMed  Google Scholar 

  74. Buchholz AC, McGillivray CF, Pencharz PB. Differences in resting metabolic rate between paraplegic and able-bodied subjects are explained by differences in body composition. Am J Clin Nutr. 2003;77:371–8.

    CAS  PubMed  Google Scholar 

  75. Aksnes AK, Brundin T, Hjeltnes N, Maehlum S, Wahren J. Meal-induced rise in resting energy expenditure in patients with complete cervical spinal cord lesions. Paraplegia. 1993;31:462–72.

    CAS  PubMed  Google Scholar 

  76. Nevin AN, Steenson J, Vivanti A, Hickman IJ. Investigation of measured and predicted resting energy needs in adults after spinal cord injury: a systematic review. Spinal Cord. 2016;54:248–53.

    CAS  PubMed  Google Scholar 

  77. Song YG, Won YH, Park SH, Ko MH, Seo JH. Changes in body temperature in incomplete spinal cord injury by digital infrared thermographic imaging. Ann Rehabil Med. 2015;39:696–704.

    PubMed  PubMed Central  Google Scholar 

  78. Guttmann L, Silver J, Wyndham CH. Thermoregulation in spinal man. J Physiol. 1958;142:406–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Downey JA, Chiodi HP, Darling RC. Central temperature regulation in the spinal man. J Appl Physiol. 1967;22:91–4.

    CAS  PubMed  Google Scholar 

  80. Downey JA, Huckaba CE, Myers SJ, Darling RC. Thermoregulation in the spinal man. J Appl Physiol. 1973;34:790–4.

    CAS  PubMed  Google Scholar 

  81. Cinti S. The adipose organ. Prostaglandins Leukot Essent Fatty Acids. 2005;73:9–15.

    CAS  PubMed  Google Scholar 

  82. Cinti S. The role of brown adipose tissue in human obesity. Nutr Metab Cardiovasc Dis. 2006;16:569–74.

    PubMed  Google Scholar 

  83. Bartness TJ, Vaughan CH, Song CK. Sympathetic and sensory innervation of brown adipose tissue. Int J Obes (Lond.). 2010;34(Suppl 1):S36–42.

    Google Scholar 

  84. Foster DO, Depocas F, Zaror-Behrens G. Unilaterality of the sympathetic innervation of each pad of rat interscapular brown adipose tissue. Can J Physiol Pharmacol. 1982;60:107–13.

    CAS  PubMed  Google Scholar 

  85. Dulloo AG, Miller DS. Energy balance following sympathetic denervation of brown adipose tissue. Can J Physiol Pharmacol. 1984;62:235–40.

    CAS  PubMed  Google Scholar 

  86. Bartness TJ, Wade GN. Effects of interscapular brown adipose tissue denervation on body weight and energy metabolism in ovariectomized and estradiol-treated rats. Behav Neurosci. 1984;98:674–85.

    CAS  PubMed  Google Scholar 

  87. Nedergaard J, Bengtsson T, Cannon B. Three years with adult human brown adipose tissue. Ann NY Acad S Bci. 2010;1212:E20–36.

    Google Scholar 

  88. Cannon B, Nedergaard J. Yes, even human brown fat is on fire! J Clin Investig. 2012;122:486–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Cohade C, Mourtzikos KA, Wahl RL. “USA-Fat”: prevalence is related to ambient outdoor temperature-evaluation with 18F-FDG PET/CT. J Nucl Med. 2003;44:1267–70.

    PubMed  Google Scholar 

  90. Cohade C, Osman M, Pannu HK, Wahl RL. Uptake in supraclavicular area fat (“USA-Fat”): description on 18F-FDG PET/CT. J Nucl Med. 2003;44:170–6.

    CAS  PubMed  Google Scholar 

  91. Lee P, Greenfield JR, Ho KK, Fulham MJ. A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2010;299:E601–6.

    CAS  PubMed  Google Scholar 

  92. Richard D, Monge-Roffarello B, Chechi K, Labbe SM, Turcotte EE. Control and physiological determinants of sympathetically mediated brown adipose tissue thermogenesis. Front Endocrinol (Lausanne). 2012;3:36.

    Google Scholar 

  93. Carey AL, Formosa MF, Van Every EB, Bertovic D, Eikelis N, Lambert GW, Kalff V, Duffy SJ, Cherk MH, Kingwell BA. Ephedrine activates brown adipose tissue in lean but not obese humans. Diabetologia. 2013;56:147–55.

    CAS  PubMed  Google Scholar 

  94. Zingaretti MC, Crosta F, Vitali A, Guerrieri M, Frontini A, Cannon B, Nedergaard J, Cinti S. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 2009;23:3113–20.

    CAS  PubMed  Google Scholar 

  95. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360:1500–8.

    PubMed  Google Scholar 

  96. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerback S, Nuutila P. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360:1518–25.

    CAS  PubMed  Google Scholar 

  97. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360:1509–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Heaton JM. The distribution of brown adipose tissue in the human. J Anat. 1972;112:35–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Nedergaard J, Cannon B. The changed metabolic world with human brown adipose tissue: therapeutic visions. Cell Metab. 2010;11:268–72.

    CAS  PubMed  Google Scholar 

  100. Nedergaard J, Bengtsson T, Cannon B. New powers of brown fat: fighting the metabolic syndrome. Cell Metab. 2011;13:238–40.

    CAS  PubMed  Google Scholar 

  101. Landsberg L, Krieger DR. Obesity, metabolism, and the sympathetic nervous system. Am J Hypertens. 1989;2:125S–32S.

    CAS  PubMed  Google Scholar 

  102. Orava J, Nuutila P, Noponen T, Parkkola R, Viljanen T, Enerback S, Rissanen A, Pietilainen KH, Virtanen KA. Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans. Obesity (Silver Spring). 2013;21(11):2279–87.

    CAS  Google Scholar 

  103. Vijgen GH, Bouvy ND, Teule GJ, Brans B, Schrauwen P, van Marken Lichtenbelt WD. Brown adipose tissue in morbidly obese subjects. PLoS One. 2011;6:e17247.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. • Admiraal WM, Holleman F, Bahler L, Soeters MR, Hoekstra JB, Verberne HJ. Combining 123I-metaiodobenzylguanidine SPECT/CT and 18F-FDG PET/CT for the assessment of brown adipose tissue activity in humans during cold exposure. J Nucl Med. 2013;54:208–12. Demonstrated with imaging modalities a positive correlation between brown adipose tissue activity and sympathetic nervous system markers in cold-stimulated, health human subjects.

    CAS  PubMed  Google Scholar 

  105. Blondin DP, Labbe SM, Christian TH, Noll C, Kunach M, Phoenix S, Guerin B, Turcotte EE, Carpentier AC, Richard D, Haman F. Increased brown adipose tissue oxidative capacity in cold-acclimated humans. J Clin Endocrinol Metab. 2014;99:E438–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Chen KY, Brychta RJ, Linderman JD, Smith S, Courville A, Dieckmann W, Herscovitch P, Millo CM, Remaley A, Lee P, Celi FS. Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. J Clin Endocrinol Metab. 2013;98:E1218–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Cypess AM, Chen YC, Sze C, Wang K, English J, Chan O, Holman AR, Tal I, Palmer MR, Kolodny GM, Kahn CR. Cold but not sympathomimetics activates human brown adipose tissue in vivo. Proc Natl Acad Sci USA. 2012;109:10001–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Gilsanz V, Smith ML, Goodarzian F, Kim M, Wren TA, Hu HH. Changes in brown adipose tissue in boys and girls during childhood and puberty. J Pediatr. 2012;160:604–9.

    PubMed  Google Scholar 

  109. Hadi M, Chen CC, Whatley M, Pacak K, Carrasquillo JA. Brown fat imaging with (18)F-6-fluorodopamine PET/CT, (18)F-FDG PET/CT, and (123)I-MIBG SPECT: a study of patients being evaluated for pheochromocytoma. J Nucl Med. 2007;48:1077–83.

    CAS  PubMed  Google Scholar 

  110. • Matsushita M, Yoneshiro T, Aita S, Kameya T, Sugie H, Saito M. Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans. Int J Obes. (Lond.) 2014;38:812–7. Provides support for the relationship between brown adipose tissue and glucose metabolism in healthy humans.

    PubMed  Google Scholar 

  111. Nuutila P. Brown adipose tissue thermogenesis in humans. Diabetologia. 2013;56:2110–2.

    CAS  PubMed  Google Scholar 

  112. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009;58:1526–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. van Marken LW. Brown adipose tissue and the regulation of nonshivering thermogenesis. Curr Opin Clin Nutr Metab Care. 2012;15:547–52.

    Google Scholar 

  114. van Rooijen BD, van der Lans AA, Brans B, Wildberger JE, Mottaghy FM, Schrauwen P, Backes WH, van Marken Lichtenbelt WD. Imaging cold-activated brown adipose tissue using dynamic T2*-weighted magnetic resonance imaging and 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography. Investig Radiol. 2013;48:708–14.

    Google Scholar 

  115. Vijgen GH, Bouvy ND, Teule GJ, Brans B, Hoeks J, Schrauwen P, van Marken Lichtenbelt WD. Increase in brown adipose tissue activity after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2012;97:E1229–33.

    CAS  PubMed  Google Scholar 

  116. Virtanen KA, van Marken Lichtenbelt WD, Nuutila P. Brown adipose tissue functions in humans. Biochim Biophys Acta. 2013;1831:1004–8.

    CAS  PubMed  Google Scholar 

  117. Yoneshiro T, Aita S, Matsushita M, Kameya T, Nakada K, Kawai Y, Saito M. Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity (Silver Spring). 2011;19:13–6.

    Google Scholar 

  118. Yoneshiro T, Aita S, Matsushita M, Okamatsu-Ogura Y, Kameya T, Kawai Y, Miyagawa M, Tsujisaki M, Saito M. Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity (Silver Spring). 2011;19:1755–60.

    Google Scholar 

  119. Trayhurn P. Brown adipose-tissue—from thermal physiology to bioenergetics. J Biosci. 1993;18:161–73.

    CAS  Google Scholar 

  120. Cannon B, Nedergaard J. Metabolic consequences of the presence or absence of the thermogenic capacity of brown adipose tissue in mice (and probably in humans). Int J Obes (Lond.). 2010;34(Suppl 1):S7–16.

    CAS  Google Scholar 

  121. Bakker LE, Boon MR, van der Linden RA, Arias-Bouda LP, van Klinken JB, Smit F, Verberne HJ, Jukema JW, Tamsma JT, Havekes LM, van Marken Lichtenbelt WD, Jazet IM, Rensen PC. Brown adipose tissue volume in healthy lean south Asian adults compared with white Caucasians: a prospective, case-controlled observational study. Lancet Diabetes Endocrinol. 2014;2:210–7.

    PubMed  Google Scholar 

  122. • Hanssen MJ, Wierts R, Hoeks J, Gemmink A, Brans B, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD. Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance. Diabetologia 2015;58:586–95. Provides support for the relationship between brown adipose tissue function and insulin sensitivity, and its contribution to normothermia under cold exposure.

    PubMed  Google Scholar 

  123. Raiko J, Holstila M, Virtanen KA, Orava J, Saunavaara V, Niemi T, Laine J, Taittonen M, Borra RJ, Nuutila P, Parkkola R. Brown adipose tissue triglyceride content is associated with decreased insulin sensitivity, independently of age and obesity. Diabetes Obes Metab. 2015;17:516–9.

    CAS  PubMed  Google Scholar 

  124. Zhang Q, Ye H, Miao Q, Zhang Z, Wang Y, Zhu X, Zhang S, Zuo C, Zhang Z, Huang Z, Xue R, Zeng M, Huang H, Jin W, Tang Q, Guan Y, Li Y. Differences in the metabolic status of healthy adults with and without active brown adipose tissue. Wien Klin Wochenschr. 2013;125:687–95.

    CAS  PubMed  Google Scholar 

  125. • Lee P, Smith S, Linderman J, Courville AB, Brychta RJ, Dieckmann W, Werner CD, Chen KY, Celi FS. Temperature-acclimated brown adipose tissue modulates insulin sensitivity in humans. Diabetes 2014;63:3686–98. Provides support for a role of inducible brown adipose tissue in insulin sensitivity and glucose metabolism in healthy adults.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Bray GA. Obesity, a disorder of nutrient partitioning: the MONA LISA hypothesis. J Nutr. 1991;121:1146–62.

    CAS  PubMed  Google Scholar 

  127. Bray GA. Endocrine disturbances and reduced sympathetic activity in the development of obesity. Infusionstherapie. 1990;17:124–30.

    CAS  PubMed  Google Scholar 

  128. Bray GA. Obesity—a state of reduced sympathetic activity and normal or high adrenal activity (the autonomic and adrenal hypothesis revisited). Int J Obes. 1990;14(Suppl 3):77–91.

    PubMed  Google Scholar 

  129. Astrup A, Andersen T, Christensen NJ, Bulow J, Madsen J, Breum L, Quaade F. Impaired glucose-induced thermogenesis and arterial norepinephrine response persist after weight reduction in obese humans. Am J Clin Nutr. 1990;51:331–7.

    CAS  PubMed  Google Scholar 

  130. Astrup A, Buemann B, Christensen NJ, Madsen J. 24-Hour energy expenditure and sympathetic activity in postobese women consuming a high-carbohydrate diet. Am J Physiol. 1992;262:E282–8.

    CAS  PubMed  Google Scholar 

  131. Astrup AV, Christensen NJ, Breum L. Reduced plasma noradrenaline concentrations in simple-obese and diabetic obese patients. Clin Sci (Lond.). 1991;80:53–8.

    CAS  Google Scholar 

  132. Bessard T, Schutz Y, Jequier E. Energy expenditure and postprandial thermogenesis in obese women before and after weight loss. Am J Clin Nutr. 1983;38:680–93.

    CAS  PubMed  Google Scholar 

  133. Jequier E, Schutz Y. New evidence for a thermogenic defect in human obesity. Int J Obes. 1985;9(Suppl 2):1–7.

    PubMed  Google Scholar 

  134. Jequier E. Carbohydrate-induced thermogenesis in man. Int J Vitam Nutr Res. 1986;56:193–6.

    CAS  PubMed  Google Scholar 

  135. Jequier E. Energy expenditure in obesity. Clin Endocrinol Metab. 1984;13:563–80.

    CAS  PubMed  Google Scholar 

  136. Jequier E, Munger R, Felber JP. Thermogenic effects of various beta-adrenoceptor agonists in humans: their potential usefulness in the treatment of obesity. Am J Clin Nutr. 1992;55:249S–51S.

    CAS  PubMed  Google Scholar 

  137. Schutz Y, Bessard T, Jequier E. Diet-induced thermogenesis measured over a whole day in obese and nonobese women. Am J Clin Nutr. 1984;40:542–52.

    CAS  PubMed  Google Scholar 

  138. Kush RD, Young JB, Katzeff HL, Danforth E Jr., Garrow JS, Scheidegger K, Ravussin E, Howard BV, Sims EA, Horton ES. Effect of diet on energy expenditure and plasma norepinephrine in lean and obese Pima Indians. Metabolism. 1986;35:1110–20.

    CAS  PubMed  Google Scholar 

  139. Lean ME, James WP, Jennings G, Trayhurn P. Brown adipose tissue in patients with phaeochromocytoma. Int J Obes. 1986;10:219–27.

    CAS  PubMed  Google Scholar 

  140. Fukuchi K, Tatsumi M, Ishida Y, Oku N, Hatazawa J, Wahl RL. Radionuclide imaging metabolic activity of brown adipose tissue in a patient with pheochromocytoma. Exp Clin Endocrinol Diabetes. 2004;112:601–3.

    CAS  PubMed  Google Scholar 

  141. Dundamadappa SK, Shankar S, Danrad R, Singh A, Vijayaraghavan G, Kim Y, Perugini R. Imaging of brown fat associated with adrenal pheochromocytoma. Acta Radiol. 2007;48:468–72.

    CAS  PubMed  Google Scholar 

  142. Yamaga LY, Thom AF, Wagner J, Baroni RH, Hidal JT, Funari MG. The effect of catecholamines on the glucose uptake in brown adipose tissue demonstrated by (18)F-FDG PET/CT in a patient with adrenal pheochromocytoma. Eur J Nucl Med Mol Imaging. 2008;35:446–7.

    PubMed  Google Scholar 

  143. Kuji I, Imabayashi E, Minagawa A, Matsuda H, Miyauchi T. Brown adipose tissue demonstrating intense FDG uptake in a patient with mediastinal pheochromocytoma. Ann Nucl Med. 2008;22:231–5.

    PubMed  Google Scholar 

  144. Sekizawa N, Yoshimoto T, Izumiyama H, Hirata Y. Distinct uptake of 18F-fluorodeoxyglucose by brown adipose tissue with a catecholamine-secreting tumor. Intern Med. 2010;49:2363.

    PubMed  Google Scholar 

  145. Wang Q, Zhang M, Ning G, Gu W, Su T, Xu M, Li B, Wang W. Brown adipose tissue in humans is activated by elevated plasma catecholamines levels and is inversely related to central obesity. PLoS One. 2011;6:e21006.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Wallin BG, Stjernberg L. Sympathetic activity in man after spinal cord injury. Outflow to skin below the lesion. Brain. 1984;107(Pt 1):183–98.

    PubMed  Google Scholar 

  147. Karlsson AK, Attvall S, Jansson PA, Sullivan L, Lonnroth P. Influence of the sympathetic nervous system on insulin sensitivity and adipose tissue metabolism: a study in spinal cord-injured subjects. Metabolism. 1995;44:52–8.

    CAS  PubMed  Google Scholar 

  148. Astrup A. Thermogenesis in human brown adipose tissue and skeletal muscle induced by sympathomimetic stimulation. Acta Endocrinol Suppl (Copenh.). 1986;278:1–32.

    CAS  Google Scholar 

  149. van Marken Lichtenbelt WD, Schrauwen P. Implications of nonshivering thermogenesis for energy balance regulation in humans. Am J Physiol Regul Integr Comp Physiol. 2011;301:R285–96.

    PubMed  Google Scholar 

  150. Jequier E. Thermogenesis induced by nutrients in man: its role in weight regulation. J Physiol (Paris). 1985;80:129–40.

    CAS  Google Scholar 

  151. Smith DL Jr., Yang Y, Hu HH, Zhai G, Nagy TR. Measurement of interscapular brown adipose tissue of mice in differentially housed temperatures by chemical-shift-encoded water-fat MRI. J Magn Reson Imaging. 2013;38:1425–33.

    PubMed  Google Scholar 

  152. Primeaux SD, Tong M, Holmes GM. Effects of chronic spinal cord injury on body weight and body composition in rats fed a standard chow diet. Am J Physiol Regul Integr Comp Physiol. 2007;293:R1102–9.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank UAB Center for Clinical and Translational Science (1KL2TR001419, Yarar-Fisher) and the University of Alabama at Birmingham. The opinions expressed herein are those of the authors and do not necessarily reflect the official position of any of organization with which they are affiliated.

Author information

Authors and Affiliations

  1. Department of Nutrition Sciences, University of Alabama at Birmingham, Webb 423, 1720 2nd Ave S, Birmingham, AL, 35294-3360, USA

    Daniel L. Smith Jr.

  2. Nathan Shock Center of Excellence in the Basic Biology of Aging, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Daniel L. Smith Jr.

  3. Comprehensive Center for Healthy Aging, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Daniel L. Smith Jr.

  4. Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Daniel L. Smith Jr. & Ceren Yarar-Fisher

  5. Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Shelby 503, 1825 University Blvd., Birmingham, AL, 35233, USA

    Ceren Yarar-Fisher

  6. Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Ceren Yarar-Fisher

Authors
  1. Daniel L. Smith Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ceren Yarar-Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Daniel L. Smith Jr. or Ceren Yarar-Fisher.

Ethics declarations

Conflict of Interest

Daniel L. Smith, Jr. and Ceren Yarar-Fisher declare they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This review article does not contain any new, primary data of studies with human or animal subjects performed by the authors.

Additional information

This article is part of the Topical collection on Spinal Cord Injury Rehabilitation.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Smith, D.L., Yarar-Fisher, C. Contributors to Metabolic Disease Risk Following Spinal Cord Injury. Curr Phys Med Rehabil Rep 4, 190–199 (2016). https://doi.org/10.1007/s40141-016-0124-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40141-016-0124-7

Keywords

Search

Navigation